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Visco V, Forte M, Giallauria F, D'Ambrosio L, Piccoli M, Schiattarella GG, Mancusi C, Salerno N, Cesaro A, Perrone MA, Izzo C, Loffredo FS, Bellino M, Bertero E, De Luca N, Pilichou K, Calabrò P, Manno G, De Falco E, Carrizzo A, Valenti V, Castelletti S, Spadafora L, Tourkmani N, D'Andrea A, Pacileo M, Bernardi M, Maloberti A, Simeone B, Sarto G, Frati G, Perrino C, Pedrinelli R, Filardi PP, Vecchione C, Sciarretta S, Ciccarelli M. Epigenetic mechanisms underlying the beneficial effects of cardiac rehabilitation. An overview from the working groups of "cellular and molecular biology of the heart" and "cardiac rehabilitation and cardiovascular prevention" of the Italian Society of Cardiology (SIC). Int J Cardiol 2025; 429:133166. [PMID: 40088953 DOI: 10.1016/j.ijcard.2025.133166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 03/03/2025] [Accepted: 03/12/2025] [Indexed: 03/17/2025]
Abstract
The benefits of cardiac rehabilitation (CR) have been demonstrated in patients after myocardial infarction (MI), and in patients with chronic heart failure (HF). The core components of the CR program include improvement in exercise tolerance and optimization of coronary risk factors (i.e., lipid and lipoprotein profiles, body weight, blood glucose levels, blood pressure levels, and smoking cessation). Indeed, CR has been shown to improve exercise capacity, control of cardiovascular risk factors, quality of life, hospital readmission, and mortality rates. Nonetheless, pre- and clinical CR and exercise training models are an enormous source of potential beneficial mechanisms that can be exploited for cardiac disease therapy. Consequently, in this review, we aim to explore the unique benefits of CR in HF and coronary artery disease, focusing on the epigenetic mechanisms involved and their translational relevance. These mechanisms may represent novel therapeutic targets to promote functional recovery after cardiac injury, and non-coding RNAs could be predictive biomarkers for CR success in patients.
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Affiliation(s)
- Valeria Visco
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84084 Fisciano, Italy
| | | | - Francesco Giallauria
- Department of Translational Medical Sciences, Federico II University, Naples, Italy
| | - Luca D'Ambrosio
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
| | - Mara Piccoli
- Cardiology Department, CTO Andrea Alesini Hospital, Rome, Italy
| | - Gabriele G Schiattarella
- Max Rubner Center for Cardiovascular Metabolic Renal Research, Charité -Universitätsmedizin Berlin, Berlin, Germany; Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
| | - Costantino Mancusi
- Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy
| | - Nadia Salerno
- Division of Cardiology, Department of Experimental and Clinical Medicine, Magna Graecia University, Catanzaro, Italy
| | - Arturo Cesaro
- Department of Translational Medical Sciences, Division of Cardiology, University of Campania "L. Vanvitelli", Naples, Italy
| | - Marco Alfonso Perrone
- Division of Cardiology and CardioLab, Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, 00133 Rome, Italy; Clinical Pathways and Epidemiology Unit, Bambino Gesù Children's Hospital IRCCS, 00165 Rome, Italy
| | - Carmine Izzo
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84084 Fisciano, Italy
| | - Francesco S Loffredo
- Department of Translational Medical Sciences, Division of Cardiology, University of Campania "L. Vanvitelli", Naples, Italy
| | - Michele Bellino
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84084 Fisciano, Italy
| | - Edoardo Bertero
- Department of Internal Medicine, University of Genova, Genoa, Italy; Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino - Italian IRCCS Cardiology Network, Genoa, Italy
| | - Nicola De Luca
- Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy
| | - Kalliopi Pilichou
- Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova 35128, Italy
| | - Paolo Calabrò
- Department of Translational Medical Sciences, Division of Cardiology, University of Campania "L. Vanvitelli", Naples, Italy
| | - Girolamo Manno
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE) "G. D'Alessandro", University of Palermo, Palermo, Italy
| | - Elena De Falco
- Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
| | - Albino Carrizzo
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84084 Fisciano, Italy; IRCCS Neuromed, Pozzilli, Italy
| | - Valentina Valenti
- Department of Cardiology, Santa Maria Goretti Hospital, Latina, Italy
| | - Silvia Castelletti
- Cardiology Department, Istituto Auxologico Italiano IRCCS, 20149 Milan, Italy
| | | | - Nidal Tourkmani
- Cardiology and Cardiac Rehabilitation Unit, Mons. Giosuè Calaciura Clinic, Catania, Italy; ABL, Guangzhou, China
| | - Antonello D'Andrea
- Unit of Cardiology and Intensive Coronary Care, "Umberto I" Hospital, 84014 Nocera Inferiore, Italy
| | - Mario Pacileo
- Unit of Cardiology and Intensive Coronary Care, "Umberto I" Hospital, 84014 Nocera Inferiore, Italy
| | - Marco Bernardi
- Department of Clinical, Internal Medicine, Anesthesiology and Cardiovascular Sciences, Sapienza University, Rome, Italy
| | - Alessandro Maloberti
- Cardiology IV, "A.De Gasperis" Department, Ospedale Niguarda Ca' Granda, Milan, Italy; School of Medicine and Surgery, Milano-Bicocca University, Milan, Italy
| | | | | | - Giacomo Frati
- IRCCS Neuromed, Pozzilli, Italy; Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
| | - Cinzia Perrino
- Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy
| | - Roberto Pedrinelli
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine-Cardiology Division, University of Pisa, Italy
| | | | - Carmine Vecchione
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84084 Fisciano, Italy; IRCCS Neuromed, Pozzilli, Italy
| | - Sebastiano Sciarretta
- IRCCS Neuromed, Pozzilli, Italy; Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
| | - Michele Ciccarelli
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84084 Fisciano, Italy.
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Fang Z, Raza U, Song J, Lu J, Yao S, Liu X, Zhang W, Li S. Systemic aging fuels heart failure: Molecular mechanisms and therapeutic avenues. ESC Heart Fail 2025; 12:1059-1080. [PMID: 39034866 PMCID: PMC11911610 DOI: 10.1002/ehf2.14947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 05/29/2024] [Accepted: 06/21/2024] [Indexed: 07/23/2024] Open
Abstract
Systemic aging influences various physiological processes and contributes to structural and functional decline in cardiac tissue. These alterations include an increased incidence of left ventricular hypertrophy, a decline in left ventricular diastolic function, left atrial dilation, atrial fibrillation, myocardial fibrosis and cardiac amyloidosis, elevating susceptibility to chronic heart failure (HF) in the elderly. Age-related cardiac dysfunction stems from prolonged exposure to genomic, epigenetic, oxidative, autophagic, inflammatory and regenerative stresses, along with the accumulation of senescent cells. Concurrently, age-related structural and functional changes in the vascular system, attributed to endothelial dysfunction, arterial stiffness, impaired angiogenesis, oxidative stress and inflammation, impose additional strain on the heart. Dysregulated mechanosignalling and impaired nitric oxide signalling play critical roles in the age-related vascular dysfunction associated with HF. Metabolic aging drives intricate shifts in glucose and lipid metabolism, leading to insulin resistance, mitochondrial dysfunction and lipid accumulation within cardiomyocytes. These alterations contribute to cardiac hypertrophy, fibrosis and impaired contractility, ultimately propelling HF. Systemic low-grade chronic inflammation, in conjunction with the senescence-associated secretory phenotype, aggravates cardiac dysfunction with age by promoting immune cell infiltration into the myocardium, fostering HF. This is further exacerbated by age-related comorbidities like coronary artery disease (CAD), atherosclerosis, hypertension, obesity, diabetes and chronic kidney disease (CKD). CAD and atherosclerosis induce myocardial ischaemia and adverse remodelling, while hypertension contributes to cardiac hypertrophy and fibrosis. Obesity-associated insulin resistance, inflammation and dyslipidaemia create a profibrotic cardiac environment, whereas diabetes-related metabolic disturbances further impair cardiac function. CKD-related fluid overload, electrolyte imbalances and uraemic toxins exacerbate HF through systemic inflammation and neurohormonal renin-angiotensin-aldosterone system (RAAS) activation. Recognizing aging as a modifiable process has opened avenues to target systemic aging in HF through both lifestyle interventions and therapeutics. Exercise, known for its antioxidant effects, can partly reverse pathological cardiac remodelling in the elderly by countering processes linked to age-related chronic HF, such as mitochondrial dysfunction, inflammation, senescence and declining cardiomyocyte regeneration. Dietary interventions such as plant-based and ketogenic diets, caloric restriction and macronutrient supplementation are instrumental in maintaining energy balance, reducing adiposity and addressing micronutrient and macronutrient imbalances associated with age-related HF. Therapeutic advancements targeting systemic aging in HF are underway. Key approaches include senomorphics and senolytics to limit senescence, antioxidants targeting mitochondrial stress, anti-inflammatory drugs like interleukin (IL)-1β inhibitors, metabolic rejuvenators such as nicotinamide riboside, resveratrol and sirtuin (SIRT) activators and autophagy enhancers like metformin and sodium-glucose cotransporter 2 (SGLT2) inhibitors, all of which offer potential for preserving cardiac function and alleviating the age-related HF burden.
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Affiliation(s)
- Zhuyubing Fang
- Cardiovascular Department of Internal MedicineKaramay Hospital of People's Hospital of Xinjiang Uygur Autonomous RegionKaramayXinjiang Uygur Autonomous RegionChina
| | - Umar Raza
- School of Basic Medical SciencesShenzhen UniversityShenzhenGuangdong ProvinceChina
| | - Jia Song
- Department of Medicine (Cardiovascular Research)Baylor College of MedicineHoustonTexasUSA
| | - Junyan Lu
- Department of CardiologyZengcheng Branch of Nanfang Hospital, Southern Medical UniversityGuangzhouGuangdong ProvinceChina
| | - Shun Yao
- Department of NeurosurgeryThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhouGuangdong ProvinceChina
| | - Xiaohong Liu
- Cardiovascular Department of Internal MedicineKaramay Hospital of People's Hospital of Xinjiang Uygur Autonomous RegionKaramayXinjiang Uygur Autonomous RegionChina
| | - Wei Zhang
- Outpatient Clinic of SurgeryThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhouGuangdong ProvinceChina
| | - Shujuan Li
- Department of Pediatric CardiologyThe First Affiliated Hospital, Sun Yat‐sen UniversityGuangzhouGuangdong ProvinceChina
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Wu Y, Hou M, Deng Y, Xia X, Liu Y, Yu J, Yu C, Yang H, Zhang Y, Zhu X. Swimming exercise induces redox-lipid crosstalk to ameliorate osteoarthritis progression. Redox Biol 2025; 81:103535. [PMID: 39952199 PMCID: PMC11875157 DOI: 10.1016/j.redox.2025.103535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 02/05/2025] [Accepted: 02/05/2025] [Indexed: 02/17/2025] Open
Abstract
Conventional pharmacotherapy exhibits limited efficacy in halting cartilage degeneration, whereas exercise interventions have demonstrated promising protective effects against osteoarthritis (OA), albeit with unclear underlying mechanisms. This study investigated the beneficial effects of swimming in mitigating local joint damage through the enhancement of systemic antioxidant capacity. We found that overexpression of superoxide dismutase 3 (SOD3) could promote the elimination of extracellular reactive oxygen species (ROS) and preserve the cartilage extracellular matrix (C-ECM). Conversely, genetic deletion of SOD3 accelerated the loss of C-ECM and contributed to OA due to an imbalance in extracellular oxidative stress. Further investigation revealed that SOD3 could interact with CCAAT/enhancer binding protein β (C/EBPβ), leading to the inhibition of apolipoprotein E (APOE) transcription and subsequent APOE-induced cholesterol transport. Ultimately, we developed targeted extracellular vesicles (EVs) with high cartilage affinity for efficient and precise delivery of SOD3. Overall, this study elucidated the potential of exercise for degenerative joint disorders through SOD3-mediated extracellular antioxidation and cholesterol redistribution.
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Affiliation(s)
- Yubin Wu
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, China; Orthopaedic Institute, Medical College, Soochow University, Suzhou, 215000, China
| | - Mingzhuang Hou
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, China; Orthopaedic Institute, Medical College, Soochow University, Suzhou, 215000, China
| | - Yaoge Deng
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, China; Orthopaedic Institute, Medical College, Soochow University, Suzhou, 215000, China
| | - Xiaowei Xia
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, China; Orthopaedic Institute, Medical College, Soochow University, Suzhou, 215000, China
| | - Yang Liu
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, China; Orthopaedic Institute, Medical College, Soochow University, Suzhou, 215000, China
| | - Jianfeng Yu
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, China; Orthopaedic Institute, Medical College, Soochow University, Suzhou, 215000, China
| | - Chenqi Yu
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, China; Orthopaedic Institute, Medical College, Soochow University, Suzhou, 215000, China
| | - Huilin Yang
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, China; Orthopaedic Institute, Medical College, Soochow University, Suzhou, 215000, China.
| | - Yijian Zhang
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, China; Orthopaedic Institute, Medical College, Soochow University, Suzhou, 215000, China.
| | - Xuesong Zhu
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215006, China; Orthopaedic Institute, Medical College, Soochow University, Suzhou, 215000, China.
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Fan B, Ren K, Li L. Propensity score matching analysis of the association between physical activity and multimorbidity in middle-aged and elderly Chinese. Sci Rep 2024; 14:31166. [PMID: 39732820 DOI: 10.1038/s41598-024-82335-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 12/04/2024] [Indexed: 12/30/2024] Open
Abstract
In the context of an aging population, older adults increasingly face the challenge of managing multiple chronic conditions simultaneously. This study utilized analytical methods such as propensity score matching (PSM) and multivariate logistic regression, to explore the relationship between physical activity and the number of chronic diseases as well as the risk of developing co-morbidities among middle-aged and elderly Chinese individuals using data from the 2020 China Health and Retirement Longitudinal Survey. The PSM results showed that physical activity decreased the number of chronic diseases in middle-aged and elderly people by 0.050 (p < 0.05). The multivariate logistic regression results the odds ratio (OR) for the risk of multimorbidity in the moderate and high intensity physical activity groups compared to the group with inadequate physical activity were 0.845 (95% CI 0.729-0.980) and 0.847 (95% CI 0.727-0.988), which means that moderate-intensity physical activity is strongly associated with a reduced risk of multimorbidity. Regular physical activity among middle-aged and older adults is associated with a reduction in the number of chronic diseases they suffer from.
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Affiliation(s)
- Bingbing Fan
- College of Physical Education, Jilin Normal University, Siping, 136000, Jilin, China
| | - Kexin Ren
- College of Physical Education, Jilin Normal University, Siping, 136000, Jilin, China.
| | - Lang Li
- College of Physical Education, Jilin Normal University, Siping, 136000, Jilin, China
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Jia J, Sun Z, Tao X, Tong Y, Feng H, Yang J, Lu X, Qu C, Liu Z, Wu J. Association between oxidative balance score and heart failure in the older adults: Results from the NHANES 2005-2018. Heart Lung 2024; 68:107-115. [PMID: 38943717 DOI: 10.1016/j.hrtlng.2024.06.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 05/27/2024] [Accepted: 06/11/2024] [Indexed: 07/01/2024]
Abstract
BACKGROUND Heart failure (HF) imposes a substantial burden on older adults, and healthy diets and lifestyles may bring with benefits. However, quantifiable studies on the dietary and lifestyle risk factors for HF are scant. The Oxidative Balance Score (OBS) reflects the oxidative stress status of dietary components and lifestyle factors, but its relationship with HF risk is unclear. OBJECTIVE We aims to explore the association between OBS and the prevalence of HF. METHODS Using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018, the association between OBS and the HF prevalence was analyzed by weighted logistic regression and restricted cubic splines (RCS). Subgroup and sensitivity analyses assessed the stability of the results. RESULTS The prevalence of HF in the cohort of 6238 older adults was 5.55 %. Compared to the lowest quintile, the adjusted ORs for HF in the highest quintile of OBS and lifestyle OBS were 0.57 (95 % CI: 0.33,0.97) and 0.21 (95 %CI: 0.09,0.50), respectively. The association between OBS and HF prevalence remained stable across different models and subgroups. RCS revealed a potential inflection point. Sensitivity analysis validated the negative association between OBS and HF prevalence, and the correlation analysis between OBS and serum γ-glutamyltransferase (γ-GGT) confirmed the reliability of the study design. CONCLUSION The OBS is negatively associated with HF prevalence in older adults, and may help prevent HF in this population.
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Affiliation(s)
- Jian Jia
- Department of General Practice, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China
| | - Zhonghua Sun
- Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, PR China
| | - Xinyu Tao
- Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, PR China
| | - Yanli Tong
- Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, PR China
| | - Han Feng
- Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, PR China
| | - Jiahui Yang
- Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, PR China
| | - Xiang Lu
- Department of Geriatrics, Sir Run Hospital of Nanjing Medical University, Nanjing 211166, PR China
| | - Chen Qu
- Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, PR China.
| | - Zhengxia Liu
- Department of Geriatrics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, PR China.
| | - Jun Wu
- Department of Geriatric Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
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Pan S, Ren W, Zhao Y, Cai M, Tian Z. Role of Irisin in exercise training-regulated endoplasmic reticulum stress, autophagy and myogenesis in the skeletal muscle after myocardial infarction. J Physiol Biochem 2024; 80:895-908. [PMID: 39271606 DOI: 10.1007/s13105-024-01049-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 09/05/2024] [Indexed: 09/15/2024]
Abstract
Patients with heart failure (HF) are often accompanied by skeletal muscle abnormalities, which can lead to exercise intolerance and compromise daily activities. Irisin, an exercise training (ET) -induced myokine, regulates energy metabolism and skeletal muscle homeostasis. However, the precise role of Irisin in the benefits of ET on inhibiting skeletal muscle atrophy, particularly on endoplasmic reticulum (ER) stress, autophagy, and myogenesis following myocardial infarction (MI) remains unclear. In this study, we investigated the expression of Irisin protein in wild-type mice with MI, and assessed its role in the beneficial effects of ET using an Fndc5 knockout mice. Our findings revealed that MI reduced muscle fiber cross-sectional area (CSA), while downregulating the expression of Irisin, PGC-1α and SOD1. Concurrently, MI elevated the levels of ER stress and apoptosis, and inhibited autophagy in skeletal muscle. Conversely, ET mitigated ER stress and apoptosis in the skeletal muscle of infarcted mice. Notably, Fndc5 knockout worsened MI-induced ER stress and apoptosis, suppressed autophagy and myogenesis, and abrogated the beneficial effects of ET. In conclusion, our findings highlight the role of Irisin in the ET-mediated alleviation of skeletal muscle abnormalities. This study provides valuable insights into MI-induced muscle abnormalities and enhances our understanding of exercise rehabilitation mechanisms in clinical MI patients.
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Affiliation(s)
- Shou Pan
- Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, 620 West Chang'an Avenue, Xi'an, 710119, P. R. China
| | - Wujing Ren
- Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, 620 West Chang'an Avenue, Xi'an, 710119, P. R. China
| | - Yifang Zhao
- Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, 620 West Chang'an Avenue, Xi'an, 710119, P. R. China
| | - Mengxin Cai
- Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, 620 West Chang'an Avenue, Xi'an, 710119, P. R. China.
| | - Zhenjun Tian
- Institute of Sports Biology, College of Physical Education, Shaanxi Normal University, 620 West Chang'an Avenue, Xi'an, 710119, P. R. China.
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Powers SK, Lategan-Potgieter R, Goldstein E. Exercise-induced Nrf2 activation increases antioxidant defenses in skeletal muscles. Free Radic Biol Med 2024; 224:470-478. [PMID: 39181477 DOI: 10.1016/j.freeradbiomed.2024.07.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 07/30/2024] [Indexed: 08/27/2024]
Abstract
Following the discovery that exercise increases the production of reactive oxygen species in contracting skeletal muscles, evidence quickly emerged that endurance exercise training increases the abundance of key antioxidant enzymes in the trained muscles. Since these early observations, knowledge about the impact that regular exercise has on skeletal muscle antioxidant capacity has increased significantly. Importantly, in recent years, our understanding of the cell signaling pathways responsible for this exercise-induced increase in antioxidant enzymes has expanded exponentially. Therefore, the goals of this review are: 1) summarize our knowledge about the influence that exercise training has on the abundance of key antioxidant enzymes in skeletal muscles; and 2) to provide a state-of-the-art review of the nuclear factor erythroid 2-related factor (Nrf2) signaling pathway that is responsible for many of the exercise-induced changes in muscle antioxidant capacity. We begin with a discussion of the sources of reactive oxygen species in contracting muscles and then examine the exercise-induced changes in the antioxidant enzymes that eliminate both superoxide radicals and hydrogen peroxide in muscle fibers. We conclude with a discussion of the advances in our understanding of the exercise-induced control of the Nrf2 signaling pathway that is responsible for the expression of numerous antioxidant proteins. In hopes of stimulating future research, we also identify gaps in our knowledge about the signaling pathways responsible for the exercise-induced increases in muscle antioxidant enzymes.
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Affiliation(s)
- Scott K Powers
- Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA.
| | | | - Erica Goldstein
- Department of Health Sciences, Stetson University, Deland, FL, USA
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Chaudhari M, Zelko I, Lorkiewicz P, Hoetker D, Nong Y, Doelling B, Brittian K, Bhatnagar A, Srivastava S, Baba SP. Metabolic pathways for removing reactive aldehydes are diminished in the skeletal muscle during heart failure. Skelet Muscle 2024; 14:24. [PMID: 39425168 PMCID: PMC11488087 DOI: 10.1186/s13395-024-00354-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 09/25/2024] [Indexed: 10/21/2024] Open
Abstract
Muscle wasting is a serious complication in heart failure patients. Oxidative stress and inflammation are implicated in the pathogenesis of muscle wasting. Oxidative stress leads to the formation of toxic lipid peroxidation products, such as 4-hydroxy-2-nonenal (HNE), which covalently bind with proteins and DNA and activate atrophic pathways. Whether the formation of lipid peroxidation products and metabolic pathways that remove these toxic products are affected during heart failure-associated skeletal muscle wasting has never been studied. Male C57BL/6J mice were subjected to sham and transverse aortic constriction (TAC) surgeries for 4, 8 or 14 weeks. Different skeletal muscle beds were weighed, and the total cross-sectional area of the gastrocnemius muscle was measured via immunohistochemistry. Muscle function and muscle stiffness were measured by a grip strength meter and atomic force microscope, respectively. Atrophic and inflammatory marker levels were measured via qRT‒PCR. The levels of acrolein and HNE-protein adducts, aldehyde-removing enzymes, the histidyl dipeptide-synthesizing enzyme carnosine synthase (CARNS), and amino acid transporters in the gastrocnemius muscle were measured via Western blotting and qRT‒PCR. Histidyl dipeptides and histidyl dipeptide aldehyde conjugates in the Gastrocnemius and soleus muscles were analyzed by LC/MS-MS. Body weight, gastrocnemius muscle and soleus muscle weights and the total cross-sectional area of the gastrocnemius muscle were decreased after 14 weeks of TAC. Heart weight, cardiac function, grip strength and muscle stiffness were decreased in the TAC-operated mice. Expression of the atrophic and inflammatory markers Atrogin1 and TNF-α, respectively, was increased ~ 1.5-2fold in the gastrocnemius muscle after 14 weeks of TAC (p < 0.05 and p = 0.004 vs sham). The formation of HNE and acrolein protein adducts was increased, and the expression of the aldehyde-removing enzyme aldehyde dehydrogenase (ALDH2) was decreased in the gastrocnemius muscle of TAC mice. Carnosine (sham: 5.76 ± 1.3 vs TAC: 4.72 ± 0.7 nmol/mg tissue, p = 0.04) and total histidyl dipeptide levels (carnosine and anserine; sham: 11.97 ± 1.5 vs TAC: 10.13 ± 1.4 nmol/mg tissue, p < 0.05) were decreased in the gastrocnemius muscle of TAC mice. Depletion of histidyl dipeptides diminished the aldehyde removal capacity of the atrophic gastrocnemius muscle. Furthermore, CARNS and TAUT protein expression were decreased in the atrophic gastrocnemius muscle. Our data reveals that reduced expression of ALDH2 and depletion of histidyl dipeptides in the gastrocnemius muscle during heart failure leads to the accumulation of toxic aldehydes and might contribute to muscle wasting.
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Affiliation(s)
- Mamata Chaudhari
- Center for Cardiometabolic Science, Louisville, KY, USA
- Department of Medicine, Christina Lee Brown Envirome Institute, University of Louisville, 580 South Preston Street, Delia Baxter Building, Room 304A, Louisville, KY, 40202, USA
| | - Igor Zelko
- Center for Cardiometabolic Science, Louisville, KY, USA
- Department of Medicine, Christina Lee Brown Envirome Institute, University of Louisville, 580 South Preston Street, Delia Baxter Building, Room 304A, Louisville, KY, 40202, USA
| | - Pawel Lorkiewicz
- Center for Cardiometabolic Science, Louisville, KY, USA
- Department of Medicine, Christina Lee Brown Envirome Institute, University of Louisville, 580 South Preston Street, Delia Baxter Building, Room 304A, Louisville, KY, 40202, USA
| | - David Hoetker
- Center for Cardiometabolic Science, Louisville, KY, USA
- Department of Medicine, Christina Lee Brown Envirome Institute, University of Louisville, 580 South Preston Street, Delia Baxter Building, Room 304A, Louisville, KY, 40202, USA
| | - Yibing Nong
- Center for Cardiometabolic Science, Louisville, KY, USA
- Department of Medicine, Christina Lee Brown Envirome Institute, University of Louisville, 580 South Preston Street, Delia Baxter Building, Room 304A, Louisville, KY, 40202, USA
| | - Benjamin Doelling
- Center for Cardiometabolic Science, Louisville, KY, USA
- Department of Medicine, Christina Lee Brown Envirome Institute, University of Louisville, 580 South Preston Street, Delia Baxter Building, Room 304A, Louisville, KY, 40202, USA
| | - Kenneth Brittian
- Center for Cardiometabolic Science, Louisville, KY, USA
- Department of Medicine, Christina Lee Brown Envirome Institute, University of Louisville, 580 South Preston Street, Delia Baxter Building, Room 304A, Louisville, KY, 40202, USA
| | - Aruni Bhatnagar
- Center for Cardiometabolic Science, Louisville, KY, USA
- Department of Medicine, Christina Lee Brown Envirome Institute, University of Louisville, 580 South Preston Street, Delia Baxter Building, Room 304A, Louisville, KY, 40202, USA
| | | | - Shahid P Baba
- Center for Cardiometabolic Science, Louisville, KY, USA.
- Department of Medicine, Christina Lee Brown Envirome Institute, University of Louisville, 580 South Preston Street, Delia Baxter Building, Room 304A, Louisville, KY, 40202, USA.
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9
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Stojiljković S, Gavrilović L, Pejić S, Pajović SB, Macura M, Nikolić D, Bubanj S, Stojiljković V. Effects of Endurance Training on Antioxidant and Hormonal Status in Peripheral Blood of Young Healthy Men. Life (Basel) 2024; 14:921. [PMID: 39202664 PMCID: PMC11355762 DOI: 10.3390/life14080921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 07/16/2024] [Accepted: 07/23/2024] [Indexed: 09/03/2024] Open
Abstract
(1) Background: Physical activity may cause an imbalance in the major functions of the human body. This study aimed to investigate the effects of endurance running training on the parameters of the antioxidant defense system (SOD, CAT, GPx, GR, GSH), LPO (malondialdehyde, MDA), and stress hormones (A, NA) in young healthy, previously untrained men. (2) Methods: The training program was as follows: 8 weeks of running, three times per week; the duration of a single session was 30-70 min, the intensity was twice a week in the so-called extensive endurance zone, and once a week in the anaerobic threshold zone. Blood samples were collected from the subjects, before and after the running program. (3) Results: The training program resulted in a significant increase in maximal oxygen consumption (p < 0.001). The activities of SOD, GPx, and GR also increased significantly (p < 0.05, p < 0.01, and p < 0.05, respectively), while CAT activity and GSH and MDA concentrations remained unchanged. The concentration of A decreased (p < 0.05), while the NA concentration increased significantly (p < 0.05). SOD, GPx, GR, and NA positively correlated with VO2max (p < 0.05, p < 0.001, p < 0.01, p < 0.05, respectively), while a negative correlation was detected between A and VO2max (p < 0.05). (4) Conclusions: These results indicate that there is no persistent oxidative stress in response to the applied 8-week running program, probably due to exercise-induced protective alterations in the antioxidant defense system. Furthermore, adaptations occurred at the hormonal level, making the organism more ready for a new challenge.
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Affiliation(s)
- Stanimir Stojiljković
- Faculty of Sport and Physical Education, University of Belgrade, 11000 Belgrade, Serbia; (S.S.); (M.M.)
| | - Ljubica Gavrilović
- Department of Molecular Biology and Endocrinology, “Vinča” Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia; (L.G.); (S.P.); (S.B.P.)
| | - Snežana Pejić
- Department of Molecular Biology and Endocrinology, “Vinča” Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia; (L.G.); (S.P.); (S.B.P.)
| | - Snežana B. Pajović
- Department of Molecular Biology and Endocrinology, “Vinča” Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia; (L.G.); (S.P.); (S.B.P.)
| | - Marija Macura
- Faculty of Sport and Physical Education, University of Belgrade, 11000 Belgrade, Serbia; (S.S.); (M.M.)
| | - Dragan Nikolić
- School of Medicine, University of Belgrade, 11000 Belgrade, Serbia;
- Clinic for Endocrinology, Diabetes and Metabolic Diseases (Laboratory for Cells Culture), Clinical Centre of Serbia, 11000 Belgrade, Serbia
| | - Saša Bubanj
- Faculty of Sport and Physical Education, University of Niš, 18000 Niš, Serbia;
| | - Vesna Stojiljković
- Department of Molecular Biology and Endocrinology, “Vinča” Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia; (L.G.); (S.P.); (S.B.P.)
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10
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Wernhart S, Rassaf T. Relevance of Cardiovascular Exercise in Cancer and Cancer Therapy-Related Cardiac Dysfunction. Curr Heart Fail Rep 2024; 21:238-251. [PMID: 38696059 PMCID: PMC11090948 DOI: 10.1007/s11897-024-00662-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/03/2024] [Indexed: 05/14/2024]
Abstract
PURPOSE OF THE REVIEW Cancer therapy-related cardiac dysfunction (CTRCD) has been identified as a threat to overall and cancer-related survival. Although aerobic exercise training (AET) has been shown to improve cardiorespiratory fitness (CRF), the relationship between specific exercise regimens and cancer survival, heart failure development, and reduction of CTRCD is unclear. In this review, we discuss the impact of AET on molecular pathways and the current literature of sports in the field of cardio-oncology. RECENT FINDINGS Cardio-oncological exercise trials have focused on variations of AET intensity by using moderate continuous and high intensity interval training, which are applicable, safe, and effective approaches to improve CRF. AET increases CRF, reduces cardiovascular morbidity and heart failure hospitalization and should thus be implemented as an adjunct to standard cancer therapy, although its long-term effect on CTRCD remains unknown. Despite modulating diverse molecular pathways, it remains unknown which exercise regimen, including variations of AET duration and frequency, is most suited to facilitate peripheral and central adaptations to exercise and improve survival in cancer patients.
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Affiliation(s)
- Simon Wernhart
- Department of Cardiology and Vascular Medicine, West German Heart- and Vascular Center, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany.
| | - Tienush Rassaf
- Department of Cardiology and Vascular Medicine, West German Heart- and Vascular Center, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45147, Essen, Germany
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11
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Zhang Q, Chen W, Li G, Ma Z, Zhu M, Gao Q, Xu K, Liu X, Lu W, Zhang W, Wu Y, Shi Z, Su J. A Factor-Free Hydrogel with ROS Scavenging and Responsive Degradation for Enhanced Diabetic Bone Healing. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2306389. [PMID: 38168513 DOI: 10.1002/smll.202306389] [Citation(s) in RCA: 21] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Revised: 11/27/2023] [Indexed: 01/05/2024]
Abstract
In view of the increased levels of reactive oxygen species (ROS) that disturb the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), the repair of diabetic bone defects remains a great challenge. Herein, a factor-free hydrogel is reported with ROS scavenging and responsive degradation properties for enhanced diabetic bone healing. These hydrogels contain ROS-cleavable thioketal (TK) linkers and ultraviolet (UV)-responsive norbornene (NB) groups conjugated with 8-arm PEG macromers, which are formed via UV crosslinking-mediated gelation. Upon reacting with high levels of ROS in the bone defect microenvironment, ROS-cleavable TK linkers are destroyed, allowing the responsive degradation of hydrogels, which promotes the migration of BMSCs. Moreover, ROS levels are reduced through hydrogel-mediated ROS scavenging to reverse BMSC differentiation from adipogenic to osteogenic phenotype. As such, a favorable microenvironment is created after simultaneous ROS scavenging and hydrogel degradation, leading to the effective repair of bone defects in diabetic mouse models, even without the addition of growth factors. Thus, this study presents a responsive hydrogel platform that regulates ROS scavenging and stromal degradation in bone engineering.
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Affiliation(s)
- Qin Zhang
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Organoid Research Center, Shanghai University, Shanghai, 200444, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
| | - Weikai Chen
- Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hosptial of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China
| | - Guangfeng Li
- Department of Orthopedics, Shanghai Zhongye Hospital, Shanghai, 200941, China
| | - Zhixin Ma
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Organoid Research Center, Shanghai University, Shanghai, 200444, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
| | - Mengru Zhu
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Organoid Research Center, Shanghai University, Shanghai, 200444, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
| | - Qianmin Gao
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Organoid Research Center, Shanghai University, Shanghai, 200444, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
| | - Ke Xu
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Organoid Research Center, Shanghai University, Shanghai, 200444, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
| | - Xinru Liu
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Organoid Research Center, Shanghai University, Shanghai, 200444, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
| | - Wenyi Lu
- Binzhou Institute of Technology, Binzhou, Shandong, 256606, China
| | - Wencai Zhang
- Department of Orthopedics, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510630, China
| | - Yan Wu
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Organoid Research Center, Shanghai University, Shanghai, 200444, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
| | - Zhongmin Shi
- National Center for Orthopaedics, Shanghai Sixth People's Hospital, Shanghai, 200233, China
- Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai, 200233, China
| | - Jiacan Su
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
- Organoid Research Center, Shanghai University, Shanghai, 200444, China
- National Center for Translational Medicine (Shanghai) SHU Branch, Shanghai University, Shanghai, 200444, China
- Department of Orthopedics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
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12
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García-Giménez JL, Cánovas-Cervera I, Pallardó FV. Oxidative stress and metabolism meet epigenetic modulation in physical exercise. Free Radic Biol Med 2024; 213:123-137. [PMID: 38199289 DOI: 10.1016/j.freeradbiomed.2024.01.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 01/04/2024] [Accepted: 01/06/2024] [Indexed: 01/12/2024]
Abstract
Physical exercise is established as an important factor of health and generally is recommended for its positive effects on several tissues, organs, and systems. These positive effects come from metabolic adaptations that also include oxidative eustress, in which physical activity increases ROS production and antioxidant mechanisms, although this depends on the intensity of the exercise. Muscle metabolism through mechanisms such as aerobic and anaerobic glycolysis, tricarboxylic acid cycle, and oxidative lipid metabolism can produce metabolites and co-factors which directly impact the epigenetic machinery. In this review, we clearly reinforce the evidence that exercise regulates several epigenetic mechanisms and explain how these mechanisms can be regulated by metabolic products and co-factors produced during exercise. In fact, recent evidence has demonstrated the importance of epigenetics in the gene expression changes implicated in metabolic adaptation after exercise. Importantly, intermediates of the metabolism generated by continuous, acute, moderate, or strenuous exercise control the activity of epigenetic enzymes, therefore turning on or turning off the gene expression of specific programs which can lead to physiological adaptations after exercise.
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Affiliation(s)
- José Luis García-Giménez
- Faculty of Medicine and Dentistry, Department of Physiology, University of Valencia, Av/Blasco Ibañez, 15, Valencia, 46010, Spain; Biomedical Research Institute INCLIVA, Av/Menéndez Pelayo. 4acc, Valencia, 46010, Spain; CIBERER, The Centre for Biomedical Network Research on Rare Diseases, ISCIII, C. de Melchor Fernández Almagro, 3, 28029, Madrid, Spain.
| | - Irene Cánovas-Cervera
- Faculty of Medicine and Dentistry, Department of Physiology, University of Valencia, Av/Blasco Ibañez, 15, Valencia, 46010, Spain; Biomedical Research Institute INCLIVA, Av/Menéndez Pelayo. 4acc, Valencia, 46010, Spain.
| | - Federico V Pallardó
- Faculty of Medicine and Dentistry, Department of Physiology, University of Valencia, Av/Blasco Ibañez, 15, Valencia, 46010, Spain; Biomedical Research Institute INCLIVA, Av/Menéndez Pelayo. 4acc, Valencia, 46010, Spain; CIBERER, The Centre for Biomedical Network Research on Rare Diseases, ISCIII, C. de Melchor Fernández Almagro, 3, 28029, Madrid, Spain.
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13
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Aispuru-Lanche R, Jayo-Montoya JA, Maldonado-Martín S. Vascular-endothelial adaptations following low and high volumes of high-intensity interval training in patients after myocardial infarction. Ther Adv Cardiovasc Dis 2024; 18:17539447241286036. [PMID: 39380195 PMCID: PMC11483797 DOI: 10.1177/17539447241286036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Accepted: 09/04/2024] [Indexed: 10/10/2024] Open
Abstract
BACKGROUND Determinants of coronary artery disease, such as endothelial dysfunction and oxidative stress, could be attenuated by high-intensity aerobic interval exercise training (HIIT). However, the volume of this type of training is not well established. OBJECTIVE To assess the impact of two volumes of HIIT, low (LV-HIIT, <10 min at high intensity) and high (HV-HIIT, >10 min at high intensity), on vascular-endothelial function in individuals after an acute myocardial infarction (AMI). MATERIALS AND METHODS Clinical trial in 80 AMI patients (58.4 ± 8.3 years, 82.5% men) with three study groups: LV-HIIT (n = 28) and HV-HIIT (n = 28) with two sessions per week for 16 weeks and control group (CG, n = 24) with unsupervised physical activity recommendations. Endothelial function (brachial flow-mediated dilation, FMD), atherosclerosis (carotid intima-media thickness ultrasound, cIMT), and levels of oxidized low-density lipoprotein (ox-LDL) as a marker of oxidative stress were determined before and after the intervention period. RESULTS After the intervention, in the exercise groups, there was an increase in FMD (LV-HIIT, ↑58.8%; HV-HIIT, ↑94.1%; p < 0.001) concurrently with a decrease in cIMT (LV-HIIT, ↓3.0%; HV-HIIT, ↓3.2%; p = 0.019) and LDLox (LV-HIIT, ↓5.2%; HV-HIIT, ↓8.9%; p < 0.001), with no significant changes in the CG. Furthermore, a significant inverse correlation was observed between ox-LDL and endothelial function related to the volume of HIIT training performed (LV-HIIT: r = -0.376, p = 0.031; HV-HIIT: r = -0.490, p < 0.004), with no significance in the CG (r = 0.021, p = 0.924). CONCLUSION In post-AMI patients, HIIT may lead to a volume-dependent enhancement in endothelial function, attributed to a decrease in oxidative stress, with added beneficial effects in reducing vascular wall thickness. An LV-HIIT program, with less than 10 min at high intensity per session, has proven enough efficiency to initiate favorable vascular-endothelial adaptations, potentially reducing cardiovascular risk among patients with coronary artery disease. TRIAL REGISTRATION INTERFARCT, ClinicalTrials.gov: NCT02876952.
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Affiliation(s)
- Rodrigo Aispuru-Lanche
- Department of Physical Education and Sport, Faculty of Education and Sport—Physical Activity and Sport Sciences Section, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Araba, Spain
| | - Jon Ander Jayo-Montoya
- Department of Physical Education and Sport, Faculty of Education and Sport—Physical Activity and Sport Sciences Section, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Araba, Spain
| | - Sara Maldonado-Martín
- GIzartea, Kirola eta Ariketa Fisikoa Ikerkuntza Taldea (GIKAFIT), Society, Sports, and Physical Exercise Research Group, Department of Physical Education and Sport, Faculty of Education and Sport—Physical Activity and Sport Sciences Section, University of the Basque Country (UPV/EHU), Portal de Lasarte, 71, Vitoria-Gasteiz, Araba 01007, Spain
- Physical Activity, Exercise, and Health Group, Bioaraba Health Research Institute, Vitoria-Gasteiz, Araba, Spain
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14
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De Luca M, Crisci G, Armentaro G, Cicco S, Talerico G, Bobbio E, Lanzafame L, Green CG, McLellan AG, Debiec R, Caferra P, Scicali R, Cannatà A, Israr MZ, Heaney LM, Salzano A. Endothelial Dysfunction and Heart Failure with Preserved Ejection Fraction-An Updated Review of the Literature. Life (Basel) 2023; 14:30. [PMID: 38255646 PMCID: PMC10817572 DOI: 10.3390/life14010030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 12/11/2023] [Accepted: 12/14/2023] [Indexed: 01/24/2024] Open
Abstract
Heart failure (HF) is a clinical syndrome consisting of typical symptoms and signs due to structural and/or functional abnormalities of the heart, resulting in elevated intracardiac pressures and/or inadequate cardiac output. The vascular system plays a crucial role in the development and progression of HF regardless of ejection fraction, with endothelial dysfunction (ED) as one of the principal features of HF. The main ED manifestations (i.e., impaired endothelium-dependent vasodilation, increased oxidative stress, chronic inflammation, leukocyte adhesion, and endothelial cell senescence) affect the systemic and pulmonary haemodynamic and the renal and coronary circulation. The present review is aimed to discuss the contribution of ED to HF pathophysiology-in particular, HF with preserved ejection fraction-ED role in HF patients, and the possible effects of pharmacological and non-pharmacological approaches. For this purpose, relevant data from a literature search (PubMed, Scopus, EMBASE, and Medline) were reviewed. As a result, ED, assessed via venous occlusion plethysmography or flow-mediated dilation, was shown to be independently associated with poor outcomes in HF patients (e.g., mortality, cardiovascular events, and hospitalization due to worsening HF). In addition, SGLT2 inhibitors, endothelin antagonists, endothelial nitric oxide synthase cofactors, antioxidants, and exercise training were shown to positively modulate ED in HF. Despite the need for future research to better clarify the role of the vascular endothelium in HF, ED represents an interesting and promising potential therapeutic target.
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Affiliation(s)
- Mariarosaria De Luca
- Department of Translational Medical Sciences, Federico II University, 80131 Naples, Italy
- Italian Clinical Outcome Research and Reporting Program (I-CORRP), 80131 Naples, Italy
| | - Giulia Crisci
- Department of Translational Medical Sciences, Federico II University, 80131 Naples, Italy
- Italian Clinical Outcome Research and Reporting Program (I-CORRP), 80131 Naples, Italy
| | - Giuseppe Armentaro
- Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Campus Universitario di Germaneto, V.le Europa, 88100 Catanzaro, Italy
| | - Sebastiano Cicco
- Internal Medicine Unit “Guido Baccelli” and Arterial Hypertension Unit “Anna Maria Pirrelli”, Department of Precision and Regenerative Medicine and Jonic Area (DiMePReJ), University of Bari Aldo Moro, Azienda Ospedaliero-Universitaria Policlinico, 70124 Bari, Italy
| | | | - Emanuele Bobbio
- Department of Cardiology, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden
- Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Kuggen, 417 56 Gothenburg, Sweden
| | - Lorena Lanzafame
- Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Christopher G. Green
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough LE11 3TU, UK
| | - Abbie G. McLellan
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough LE11 3TU, UK
| | - Radek Debiec
- Department of Cardiovascular Sciences, University of Leicester, Leicester (UK), IHR Leicester Biomedical Research Centre, Groby Road, Leicester LE3 9QP, UK
| | - Paolo Caferra
- Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
| | - Roberto Scicali
- Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy
| | - Antonio Cannatà
- Department of Cardiology, King’s College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK
- Department of Cardiovascular Sciences, Faculty of Life Sciences & Medicine, King’s College, London SE1 8WA, UK
| | - Muhammad Zubair Israr
- Department of Cardiovascular Sciences, University of Leicester, Leicester (UK), IHR Leicester Biomedical Research Centre, Groby Road, Leicester LE3 9QP, UK
| | - Liam M. Heaney
- School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough LE11 3TU, UK
| | - Andrea Salzano
- Cardiac Unit, AORN A Cardarelli, 80131 Naples, Italy
- Cardiac Unit, University Hospital of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK
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15
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Chaudhari M, Zelko I, Lorkiewicz P, Hoetker D, Doelling B, Brittian K, Bhatnagar A, Srivastava S, Baba SP. Metabolic Pathways for Removing Reactive Aldehydes are Diminished in Atrophic Muscle During Heart Failure. RESEARCH SQUARE 2023:rs.3.rs-3621159. [PMID: 38045249 PMCID: PMC10690332 DOI: 10.21203/rs.3.rs-3621159/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/05/2023]
Abstract
Background Muscle wasting is a serious complication in heart failure patients, and oxidative stress is involved in the pathogenesis of muscle wasting. Oxidative stress leads to the formation of toxic lipid peroxidation products, such as 4-hydroxy-2-nonenal (HNE) and acrolein, which causemuscle wasting. In tissues, these toxic aldehydes are metabolically removed by enzymes such asaldo keto reductases and endogenous nucleophiles, such as glutathione and carnosine. Whether these metabolic pathways could be affected in skeletal muscle during heart failure has never been studied. Methods Male wild-type C57BL/6J mice were subjected to a pressure overload model of hypertrophy by transaortic constriction (TAC) surgery, and echocardiography was performed after 14 weeks. Different skeletal muscle beds were weighed and analyzed for atrophic and inflammatory markers, Atrogin1 and TRIM63, TNF-α and IL-6, respectively, by RT-PCR. Levels of acrolein and HNE-protein adducts, aldehyde-removing enzymes, aldose reductase (AKR1B1) and aldehyde dehydrogenase 2 (ALDH2) were measured by Western blotting, and histidyl dipeptides and histidyl dipeptide aldehyde conjugates were analyzed by LC/MS-MS in the gastrocnemius and soleus muscles of sham- and TAC-operated mice. Furthermore, histidyl dipeptide synthesizing enzyme carnosine synthase (CARNS) and amino acid transporters (PEPT2 and TAUT)wasmeasured in the gastrocnemius muscles of the sham and TAC-operated mice. Results TAC-induced heart failure decreases body weight and gastrocnemius and soleus muscle weights. The expression of the atrophic and inflammatory markers Atrogin1 and TNF-α, respectively, wasincreased (~1.5-2-fold), and the formation of HNE and acrolein-protein adducts was increased in the gastrocnemius muscle of TAC-operated mice. The expression of AKR1B1 remained unchanged, whereas ALDH2 was decreased, in the gastrocnemius muscle of TAC mice. Similarly, in the atrophic gastrocnemius muscle, levels of total histidyl dipeptides (carnosine and anserine) and, in particular,carnosine were decreased. Depletion of histidyl dipeptides diminished the aldehyde removal capacity of the atrophic gastrocnemius muscle. Furthermore, the expression of CARNS and TAUT wasdecreased in the atrophic gastrocnemius muscle. Conclusions Collectively, these results show that metabolic pathways involved in the removal of lipid peroxidation products and synthesis of histidyl dipeptides are diminished in atrophic skeletal muscle during heart failure, which could contribute to muscle atrophy.
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16
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Mangner N, Winzer EB, Linke A, Adams V. Locomotor and respiratory muscle abnormalities in HFrEF and HFpEF. Front Cardiovasc Med 2023; 10:1149065. [PMID: 37965088 PMCID: PMC10641491 DOI: 10.3389/fcvm.2023.1149065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Accepted: 10/02/2023] [Indexed: 11/16/2023] Open
Abstract
Heart failure (HF) is a chronic and progressive syndrome affecting worldwide billions of patients. Exercise intolerance and early fatigue are hallmarks of HF patients either with a reduced (HFrEF) or a preserved (HFpEF) ejection fraction. Alterations of the skeletal muscle contribute to exercise intolerance in HF. This review will provide a contemporary summary of the clinical and molecular alterations currently known to occur in the skeletal muscles of both HFrEF and HFpEF, and thereby differentiate the effects on locomotor and respiratory muscles, in particular the diaphragm. Moreover, current and future therapeutic options to address skeletal muscle weakness will be discussed focusing mainly on the effects of exercise training.
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Affiliation(s)
- Norman Mangner
- Department of Internal Medicine and Cardiology, Heart Center Dresden, Technische Universität Dresden, Dresden, Germany
| | - Ephraim B. Winzer
- Department of Internal Medicine and Cardiology, Heart Center Dresden, Technische Universität Dresden, Dresden, Germany
| | - Axel Linke
- Department of Internal Medicine and Cardiology, Heart Center Dresden, Technische Universität Dresden, Dresden, Germany
| | - Volker Adams
- Laboratory of Molecular and Experimental Cardiology, Heart Center Dresden, Technische Universität Dresden, Dresden, Germany
- Dresden Cardiovascular Research Institute and Core Laboratories GmbH, Dresden, Germany
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17
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Gallagher H, Hendrickse PW, Pereira MG, Bowen TS. Skeletal muscle atrophy, regeneration, and dysfunction in heart failure: Impact of exercise training. JOURNAL OF SPORT AND HEALTH SCIENCE 2023; 12:557-567. [PMID: 37040849 PMCID: PMC10466197 DOI: 10.1016/j.jshs.2023.04.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 11/30/2022] [Accepted: 02/20/2023] [Indexed: 05/31/2023]
Abstract
This review highlights some established and some more contemporary mechanisms responsible for heart failure (HF)-induced skeletal muscle wasting and weakness. We first describe the effects of HF on the relationship between protein synthesis and degradation rates, which determine muscle mass, the involvement of the satellite cells for continual muscle regeneration, and changes in myofiber calcium homeostasis linked to contractile dysfunction. We then highlight key mechanistic effects of both aerobic and resistance exercise training on skeletal muscle in HF and outline its application as a beneficial treatment. Overall, HF causes multiple impairments related to autophagy, anabolic-catabolic signaling, satellite cell proliferation, and calcium homeostasis, which together promote fiber atrophy, contractile dysfunction, and impaired regeneration. Although both wasting and weakness are partly rescued by aerobic and resistance exercise training in HF, the effects of satellite cell dynamics remain poorly explored.
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Affiliation(s)
- Harrison Gallagher
- School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
| | - Paul W Hendrickse
- School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
| | - Marcelo G Pereira
- School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
| | - T Scott Bowen
- School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
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18
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Malandish A, Gulati M. The impacts of exercise interventions on inflammaging markers in overweight/obesity patients with heart failure: A systematic review and meta-analysis of randomized controlled trials. IJC HEART & VASCULATURE 2023; 47:101234. [PMID: 37416483 PMCID: PMC10320319 DOI: 10.1016/j.ijcha.2023.101234] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/22/2023] [Accepted: 06/18/2023] [Indexed: 07/08/2023]
Abstract
Objectives The purpose of this meta-analysis was to investigate the association of aerobic, resistance and concurrent exercises vs. control group on inflammaging markers [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1-beta, IL-8, and high sensitivity C-reactive protein (hs-CRP)] in overweight or obesity patients with heart failure (HF). Methods The databases of Scopus, PubMed, Web of Science and Google Scholar were searched until August 31, 2022 for exercise interventions vs. control group on circulating inflammaging markers in patients with HF. Only randomized controlled trial (RCT) articles were included. Standardized mean difference (SMD) and 95% confidence intervals (95%CIs) were calculated (registration code = CRD42022347164). Results Forty-six full-text articles (57 intervention arms and 3693 participants) were included. A significant reduction was occurred in inflammaging markers of IL-6 [SMD-0.205(95% CI:-0.332 to -0.078),p = 0.002] and hs-CRP [SMD -0.379 (95% CI:-0.556 to -0.202), p = 0.001] with exercise training in patients with HF. Analysis of subgroup by age, body mass index (BMI), type, intensity, duration of exercise and mean left ventricular ejection fraction (LVEF) revealed that there was a significant reduction in TNF-α for middle-aged (p = 0.031), concurrent training (p = 0.033), high intensity (p = 0.005), and heart failure with reduced ejection fraction (HFrEF) (p = 0.007) compared to the control group. There was a significant reduction in IL-6 for middle-aged (p = 0.006), overweight (p = 0.001), aerobic exercise (p = 0.001), both high and moderate intensities (p = 0.037 and p = 0.034), short-term follow-up (p = 0.001), and heart failure with preserved ejection fraction (HFpEF) (p = 0.001) compared to the control group. There was a significant reduction in hs-CRP for middle-aged (p = 0.004), elderly-aged (p = 0.001), overweight (p = 0.001), aerobic exercise (p = 0.001), concurrent training (p = 0.031), both high and moderate intensities (p = 0.017 and p = 0.001), short-term (p = 0.011), long-term (p = 0.049), and very long-term (p = 0.016) follow-ups, HFrEF (p = 0.003) and heart failure with mildly reduced ejection fraction (HFmrEF) (p = 0.048) compared to the control group. Conclusions The results confirmed that aerobic exercise and concurrent training interventions were effective to improve inflammaging markers of TNF-α, IL-6, and hs-CRP. These exercise-related anti-inflammaging responses were observed across ages (middle-aged and elderly-aged), exercise intensities, duration of follow-ups, and mean LVEFs (HFrEF, HFmrEF and HFpEF) in overweight patients with HF.
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Affiliation(s)
- Abbas Malandish
- Department of Exercise Physiology, Faculty of Sport Sciences, Urmia University, No. 19, Shams Tabrizi St., Velayat Ave., Keikhali Zone, Yamchi, East Azerbaijan, Urmia, Iran
| | - Martha Gulati
- Barbra Streisand Women’s Heart Center, Smidt Heart Institute, Cedars Sinai Medical Center, 127 S. San Vicente Blvd, Suite A3600, Los Angeles, CA 90048, USA
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19
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Razi O, Teixeira AM, Tartibian B, Zamani N, Knechtle B. Respiratory issues in patients with multiple sclerosis as a risk factor during SARS-CoV-2 infection: a potential role for exercise. Mol Cell Biochem 2023; 478:1533-1559. [PMID: 36411399 PMCID: PMC9684932 DOI: 10.1007/s11010-022-04610-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 11/04/2022] [Indexed: 11/23/2022]
Abstract
Coronavirus disease-2019 (COVID-19) is associated with cytokine storm and is characterized by acute respiratory distress syndrome (ARDS) and pneumonia problems. The respiratory system is a place of inappropriate activation of the immune system in people with multiple sclerosis (MS), and this may cause damage to the lung and worsen both MS and infections.The concerns for patients with multiple sclerosis are because of an enhance risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The MS patients pose challenges in this pandemic situation, because of the regulatory defect of autoreactivity of the immune system and neurological and respiratory tract symptoms. In this review, we first indicate respiratory issues associated with both diseases. Then, the main mechanisms inducing lung damages and also impairing the respiratory muscles in individuals with both diseases is discussed. At the end, the leading role of physical exercise on mitigating respiratory issues inducing mechanisms is meticulously evaluated.
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Affiliation(s)
- Omid Razi
- Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Razi University, Kermanshah, Iran
| | - Ana Maria Teixeira
- Research Center for Sport and Physical Activity, Faculty of Sport Sciences and Physical Education, University of Coimbra, Coimbra, Portugal
| | - Bakhtyar Tartibian
- Department of Exercise Physiology, Faculty of Physical Education and Sports Sciences, Allameh Tabataba’i University, Tehran, Iran
| | - Nastaran Zamani
- Department of Biology, Faculty of Science, Payame-Noor University, Tehran, Iran
| | - Beat Knechtle
- Institute of Primary Care, University of Zurich, Zurich, Switzerland
- Medbase St. Gallen Am Vadianplatz, Vadianstrasse 26, 9001 St. Gallen, Switzerland
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20
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Malandish A, Karimi A, Naderi M, Ghadamyari N, Gulati M. Impacts of Exercise Interventions on Inflammatory Markers and Vascular Adhesion Molecules in Patients With Heart Failure: A Meta-analysis of RCTs. CJC Open 2023; 5:429-453. [PMID: 37397615 PMCID: PMC10314121 DOI: 10.1016/j.cjco.2023.02.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 02/28/2023] [Indexed: 03/09/2023] Open
Abstract
Background The aim of this meta-analysis was to investigate the effects of concurrent, aerobic, and resistance exercise on markers of inflammation and vascular adhesion molecules (high-sensitivity C-reactive protein [hs-CRP], interleukin [IL]-6, tumour necrosis factor-alpha [TNF-α], soluble intercellular adhesion molecule-1 [sICAM-1], soluble vascular cell adhesion molecule-1 [sVCAM-1], fibrinogen, IL-1-β, IL-10, IL-18, and E-selectin) in patients with heart failure (HF). Methods The PubMed, Scopus, Web of Science, and Google Scholar databases were searched for dates up to August 31, 2022. Randomized controlled trial studies for exercise interventions on circulating inflammatory and vascular adhesion markers in patients with HF were included. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated. Results A total of 45 articles were included. Exercise training significantly reduced hs-CRP (SMD -0.441 [95% CI: -0.642 to -0.240], P = 0.001), IL-6 (SMD -0.158 (95% CI: -0.303 to -0.013], P = 0.032), and sICAM-1 (SMD -0.282 [95% CI: -0.477 to -0.086], P = 0.005) markers. Analysis of subgroups revealed that a significant reduction occurred in hs-CRP level for the following subgroups: middle-aged, elderly, overweight status, aerobic exercise, concurrent training, both high and moderate intensity, and short-term, long-term, and very long-term follow-up, compared to a control group (P < 0.05). A significant reduction occurred in IL-6 and sICAM-1 levels for those in the following subgroups, compared to a control group (P < 0.05): middle-aged, aerobic exercise, moderate-intensity exercise, and short-term follow-up. A reduction in TNF-α level occurred for middle-aged patients, compared to a control-group (P < 0.05). Conclusions These exercise-related changes (improved inflammation and vascular adhesion markers) as clinical benefits in general, and for exercise-based cardiac rehabilitation in a more-specific format, improve clinical evolution and survival in patients with HF of different etiologies (registration number = CRD42021271423).
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Affiliation(s)
- Abbas Malandish
- Department of Exercise Physiology, Faculty of Sport Sciences, Urmia University, Urmia, Iran
| | - Asma Karimi
- Department of Exercise Physiology, Faculty of Sport Sciences, Hakim Sabzevari University, Sabzevar, Iran
| | - Mahdi Naderi
- Department of Exercise Physiology, Faculty of Sport Sciences, Kharazmi University, Tehran, Iran
| | - Niloufar Ghadamyari
- Department of Exercise Physiology, Faculty of Sport Health Sciences, Ankara University, Ankara, Turkey
| | - Martha Gulati
- Barbra Streisand Women’s Heart Center, Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, California, USA
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21
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Dombrecht D, Van Daele U, Van Asbroeck B, Schieffelers D, Guns PJ, Gebruers N, Meirte J, van Breda E. Molecular mechanisms of post-burn muscle wasting and the therapeutic potential of physical exercise. J Cachexia Sarcopenia Muscle 2023; 14:758-770. [PMID: 36760077 PMCID: PMC10067483 DOI: 10.1002/jcsm.13188] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 01/03/2023] [Accepted: 01/16/2023] [Indexed: 02/11/2023] Open
Abstract
After a severe burn injury, a systemic stress response activates metabolic and inflammatory derangements that, among other, leads to muscle mass loss (muscle wasting). These negative effects on skeletal muscle continue for several months or years and are aggravated by short-term and long-term disuse. The dynamic balance between muscle protein synthesis and muscle protein breakdown (proteolysis) is regulated by complex signalling pathways that leads to an overall negative protein balance in skeletal muscle after a burn injury. Research concerning these molecular mechanisms is still scarce and inconclusive, understanding of which, if any, molecular mechanisms contribute to muscle wasting is of fundamental importance in designing of therapeutic interventions for burn patients as well. This review not only summarizes our present knowledge of the molecular mechanisms that underpin muscle protein balance but also summarizes the effects of exercise on muscle wasting post-burn as promising strategy to counteract the detrimental effects on skeletal muscle. Future research focusing on the pathways causing post-burn muscle wasting and the different effects of exercise on them is needed to confirm this hypothesis and to lay the foundation of therapeutic strategies.
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Affiliation(s)
- Dorien Dombrecht
- Department of Rehabilitation Sciences & Physiotherapy, Research group MOVANT, Multidisciplinary Metabolic Research Unit (M2RUN), University of Antwerp, Antwerp, Belgium
| | - Ulrike Van Daele
- Department of Rehabilitation Sciences & Physiotherapy, Research group MOVANT, Multidisciplinary Metabolic Research Unit (M2RUN), University of Antwerp, Antwerp, Belgium.,Oscare, Organisation for Burns, Scar After-Care and Research, Antwerp, Belgium
| | - Birgit Van Asbroeck
- Department of Rehabilitation Sciences & Physiotherapy, Research group MOVANT, Multidisciplinary Metabolic Research Unit (M2RUN), University of Antwerp, Antwerp, Belgium
| | - David Schieffelers
- Department of Rehabilitation Sciences & Physiotherapy, Research group MOVANT, Multidisciplinary Metabolic Research Unit (M2RUN), University of Antwerp, Antwerp, Belgium
| | - Pieter-Jan Guns
- Laboratory of Physiopharmacology, University of Antwerp, Antwerp, Belgium
| | - Nick Gebruers
- Department of Rehabilitation Sciences & Physiotherapy, Research group MOVANT, Multidisciplinary Metabolic Research Unit (M2RUN), University of Antwerp, Antwerp, Belgium.,Multidisciplinary Edema Clinic, Antwerp University Hospital, Edegem, Belgium
| | - Jill Meirte
- Department of Rehabilitation Sciences & Physiotherapy, Research group MOVANT, Multidisciplinary Metabolic Research Unit (M2RUN), University of Antwerp, Antwerp, Belgium.,Oscare, Organisation for Burns, Scar After-Care and Research, Antwerp, Belgium
| | - Eric van Breda
- Department of Rehabilitation Sciences & Physiotherapy, Research group MOVANT, Multidisciplinary Metabolic Research Unit (M2RUN), University of Antwerp, Antwerp, Belgium
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22
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Jiang J, Ni L, Zhang X, Gokulnath P, Vulugundam G, Li G, Wang H, Xiao J. Moderate-Intensity Exercise Maintains Redox Homeostasis for Cardiovascular Health. Adv Biol (Weinh) 2023; 7:e2200204. [PMID: 36683183 DOI: 10.1002/adbi.202200204] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 09/27/2022] [Indexed: 01/24/2023]
Abstract
It is well known that exercise is beneficial for cardiovascular health. Oxidative stress is the common pathological basis of many cardiovascular diseases. The overproduction of free radicals, both reactive oxygen species and reactive nitrogen species, can lead to redox imbalance and exacerbate oxidative damage to the cardiovascular system. Maintaining redox homeostasis and enhancing anti-oxidative capacity are critical mechanisms by which exercise protects against cardiovascular diseases. Moderate-intensity exercise is an effective means to maintain cardiovascular redox homeostasis. Moderate-intensity exercise reduces the risk of cardiovascular disease by improving mitochondrial function and anti-oxidative capacity. It also attenuates adverse cardiac remodeling and enhances cardiac function. This paper reviews the primary mechanisms of moderate-intensity exercise-mediated redox homeostasis in the cardiovascular system. Exploring the role of exercise-mediated redox homeostasis in the cardiovascular system is of great significance to the prevention and treatment of cardiovascular diseases.
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Affiliation(s)
- Jizong Jiang
- Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China.,Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, Shanghai, 200444, China
| | - Lingyan Ni
- Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China.,Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, Shanghai, 200444, China
| | - Xinxin Zhang
- Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China.,Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, Shanghai, 200444, China
| | - Priyanka Gokulnath
- Cardiovascular Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA
| | | | - Guoping Li
- Cardiovascular Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA
| | - Hongyun Wang
- Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China.,Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, Shanghai, 200444, China
| | - Junjie Xiao
- Cardiac Regeneration and Ageing Lab, Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, 226011, China.,Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science, Shanghai University, Shanghai, 200444, China
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23
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Powers SK, Goldstein E, Schrager M, Ji LL. Exercise Training and Skeletal Muscle Antioxidant Enzymes: An Update. Antioxidants (Basel) 2022; 12:antiox12010039. [PMID: 36670901 PMCID: PMC9854578 DOI: 10.3390/antiox12010039] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2022] [Revised: 12/21/2022] [Accepted: 12/23/2022] [Indexed: 12/28/2022] Open
Abstract
The pivotal observation that muscular exercise is associated with oxidative stress in humans was first reported over 45 years ago. Soon after this landmark finding, it was discovered that contracting skeletal muscles produce oxygen radicals and other reactive species capable of oxidizing cellular biomolecules. Importantly, the failure to eliminate these oxidant molecules during exercise results in oxidation of cellular proteins and lipids. Fortuitously, muscle fibers and other cells contain endogenous antioxidant enzymes capable of eliminating oxidants. Moreover, it is now established that several modes of exercise training (e.g., resistance exercise and endurance exercise) increase the expression of numerous antioxidant enzymes that protect myocytes against exercise-induced oxidative damage. This review concisely summarizes the impact of endurance, high-intensity interval, and resistance exercise training on the activities of enzymatic antioxidants within skeletal muscles in humans and other mammals. We also discuss the evidence that exercise-induced up-regulation of cellular antioxidants reduces contraction-induced oxidative damage in skeletal muscles and has the potential to delay muscle fatigue and improve exercise performance. Finally, in hopes of stimulating further research, we also discuss gaps in our knowledge of exercise-induced changes in muscle antioxidant capacity.
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Affiliation(s)
- Scott K. Powers
- Department of Health Sciences, Stetson University, Deland, FL 32723, USA
- Correspondence:
| | - Erica Goldstein
- Department of Health Sciences, Stetson University, Deland, FL 32723, USA
| | - Matthew Schrager
- Department of Health Sciences, Stetson University, Deland, FL 32723, USA
| | - Li Li Ji
- Department of Kinesiology, University of Minnesota, St Paul, MN 55455, USA
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24
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Zhu B, Fang J, Ju Z, Chen Y, Wang L, Wang H, Xing L, Cao A. Zuogui Wan ameliorates high glucose-induced podocyte apoptosis and improves diabetic nephropathy in db/db mice. Front Pharmacol 2022; 13:991976. [PMID: 36386214 PMCID: PMC9663993 DOI: 10.3389/fphar.2022.991976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 10/14/2022] [Indexed: 11/05/2022] Open
Abstract
Zuogui Wan (ZGW), a well-known traditional Chinese medicine (TCM), has been used to nourish “Kidney-Yin” for a long time in China, implying a protective effect on the kidney. The aim of the present study is to investigate the effect of ZGW on high glucose-induced podocyte apoptosis and diabetic nephropathy (DN) in db/db mice. ZGW (1 g/kg−1/day−1) was administered intragastrically to db/db mice for 8 weeks. HPLC was used for identifying the components of ZGW, biochemical and histopathological approaches were used for evaluating its therapeutic effects, and cultured mouse podocytes were used for further exploring its underlying mechanism in vitro. ZGW improved renal function and podocyte loss and also normalized kidney reactive oxygen species production in db/db mice. The cytotoxicity of ZGW on mouse podocytes was assessed by the LDH assay. The effect of ZGW on podocyte viability and apoptosis was determined with CCK-8 and Annexin-V/PI staining by treatment with high glucose. ZGW attenuated podocyte apoptosis, and oxidative stress was detected by the peroxide-sensitive fluorescent probe 2′,7′-dichlorodihydrofluorescein diacetate (DCF-DA) staining in a dose-dependent manner. Furthermore, ZGW decreased the expression of caspase-3 and phospho-p38 in both the kidney cortex and high glucose-treated podocytes. Thus, our data from in vivo and in vitro studies demonstrated that ZGW improved renal injury in diabetes by inhibiting oxidative stress and podocyte apoptosis.
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Affiliation(s)
- Bingbing Zhu
- Department of Nephrology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ji Fang
- Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Zhengcai Ju
- Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Ying Chen
- Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Li Wang
- Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hao Wang
- Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lina Xing
- Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- *Correspondence: Lina Xing, ; Aili Cao,
| | - Aili Cao
- Department of Nephrology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Nephrology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- *Correspondence: Lina Xing, ; Aili Cao,
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25
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Becker CU, Sartório CL, Campos-Carraro C, Siqueira R, Colombo R, Zimmer A, Belló-Klein A. Exercise training decreases oxidative stress in skeletal muscle of rats with pulmonary arterial hypertension. Arch Physiol Biochem 2022; 128:1330-1338. [PMID: 32449880 DOI: 10.1080/13813455.2020.1769679] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The effects of exercise training on oxidative stress in gastrocnemius of rats with pulmonary hypertension were studied. Four groups were established: sedentary control (SC), sedentary monocrotaline (SM), trained control (TC), trained monocrotaline (TM). Exercise was applied for 4 weeks, 5 days/week, 50-60 min/session, at 60% of VO2 max. Right ventricular (RV) pressures were measured, heart and gastrocnemius were removed for morphometric/biochemical analysis. Lipid peroxidation (LPO), H2O2, GSH/GSSG, and activity/expression of antioxidant enzymes were evaluated. Increased RV hypertrophy, systolic and end-diastolic pressures (RVEDP) were observed in SM animals, and the RVEDP was decreased in TM vs. SM. H2O2, SOD-1, and LPO were higher in the SM group than in SC. In TM, H2O2 was further increased when compared to SM, with a rise in antioxidant defences and a decrease in LPO. GSH/GSSG was higher only in the TC group. Exercise induced an efficient antioxidant adaptation, preventing oxidative damage to lipids.
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Affiliation(s)
- C U Becker
- Cardiovascular Physiology Laboratory, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - C L Sartório
- Department of Physiological Sciences, Federal University of Espírito Santo (UFES), Vitória, Brazil
| | - C Campos-Carraro
- Cardiovascular Physiology Laboratory, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - R Siqueira
- Cardiovascular Physiology Laboratory, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - R Colombo
- Pharmacology and Physiology Laboratory, University of Caxias do Sul, Caxias do Sul, Brazil
| | - A Zimmer
- Cardiovascular Physiology Laboratory, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - A Belló-Klein
- Cardiovascular Physiology Laboratory, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
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Sutkowy P, Wróblewska J, Wróblewski M, Nuszkiewicz J, Modrzejewska M, Woźniak A. The Impact of Exercise on Redox Equilibrium in Cardiovascular Diseases. J Clin Med 2022; 11:jcm11164833. [PMID: 36013072 PMCID: PMC9410476 DOI: 10.3390/jcm11164833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 08/05/2022] [Accepted: 08/16/2022] [Indexed: 11/16/2022] Open
Abstract
Cardiovascular diseases constitute the most important public health problem in the world. They are characterized by inflammation and oxidative stress in the heart and blood. Physical activity is recognized as one of the best ways to prevent these diseases, and it has already been applied in treatment. Physical exercise, both aerobic and anaerobic and single and multiple, is linked to the oxidant–antioxidant imbalance; however, this leads to positive adaptive changes in, among others, the increase in antioxidant capacity. The goal of the paper was to discuss the issue of redox equilibrium in the human organism in the course of cardiovascular diseases to systemize updated knowledge in the context of exercise impacts on the organism. Antioxidant supplementation is also an important issue since antioxidant supplements still have great potential regarding their use as drugs in these diseases.
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27
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Voorrips SN, Saucedo-Orozco H, Sánchez-Aguilera PI, De Boer RA, Van der Meer P, Westenbrink BD. Could SGLT2 Inhibitors Improve Exercise Intolerance in Chronic Heart Failure? Int J Mol Sci 2022; 23:8631. [PMID: 35955784 PMCID: PMC9369142 DOI: 10.3390/ijms23158631] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/28/2022] [Accepted: 07/29/2022] [Indexed: 12/04/2022] Open
Abstract
Despite the constant improvement of therapeutical options, heart failure (HF) remains associated with high mortality and morbidity. While new developments in guideline-recommended therapies can prolong survival and postpone HF hospitalizations, impaired exercise capacity remains one of the most debilitating symptoms of HF. Exercise intolerance in HF is multifactorial in origin, as the underlying cardiovascular pathology and reactive changes in skeletal muscle composition and metabolism both contribute. Recently, sodium-related glucose transporter 2 (SGLT2) inhibitors were found to improve cardiovascular outcomes significantly. Whilst much effort has been devoted to untangling the mechanisms responsible for these cardiovascular benefits of SGLT2 inhibitors, little is known about the effect of SGLT2 inhibitors on exercise performance in HF. This review provides an overview of the pathophysiological mechanisms that are responsible for exercise intolerance in HF, elaborates on the potential SGLT2-inhibitor-mediated effects on these phenomena, and provides an up-to-date overview of existing studies on the effect of SGLT2 inhibitors on clinical outcome parameters that are relevant to the assessment of exercise capacity. Finally, current gaps in the evidence and potential future perspectives on the effects of SGLT2 inhibitors on exercise intolerance in chronic HF are discussed.
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Affiliation(s)
- Suzanne N. Voorrips
- Department of Cardiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (H.S.-O.); (P.I.S.-A.); (R.A.D.B.); (P.V.d.M.)
| | | | | | | | | | - B. Daan Westenbrink
- Department of Cardiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands; (H.S.-O.); (P.I.S.-A.); (R.A.D.B.); (P.V.d.M.)
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28
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Meta-Analysis of Physical Training on Natriuretic Peptides and Inflammation in Heart Failure. Am J Cardiol 2022; 178:60-71. [PMID: 35817596 DOI: 10.1016/j.amjcard.2022.05.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 05/18/2022] [Accepted: 05/20/2022] [Indexed: 11/24/2022]
Abstract
Physical training has been reported to attenuate myocardial stress and inflammation in heart failure (HF). We aimed to assess the impact of physical training on B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide (NT-proBNP), as well as biomarkers of inflammation-C-reactive protein, tumor necrosis factor α (TNF-α), and interleukins (ILs). A systematic electronic literature search was conducted up to May 2021 in PubMed, Cochrane Library, CINAHL, Embase, and SPORTDiscus to identify randomized clinical trials reporting associations between any formal physical training intervention and biomarker levels in patients with HF. Random-effects meta-analyses was used to calculate pooled correlations between physical training and blood biomarkers. Biomarker outcomes were expressed as mean difference or ratio of means and 95% confidence interval between the intervention and control groups, according to the normality of the data. A total of 38 trials were included in the final meta-analysis (2,652 randomized patients). Physical training was associated with decreased B-type natriuretic peptide (p = 0.02), NT-proBNP (p <0.01), C-reactive protein (p <0.00001), TNF-α (p = 0.03), IL-6 (p = 0.04), and IL-1β (p = 0.001). Aerobic continuous training was associated with a 35% reduction in NT-proBNP (p = 0.01); ≥150 min/week of exercise was associated with a greater reduction in TNF-α levels (p = 0.0004), and aerobic interval training was associated with lower IL-6 levels (p = 0.01). In conclusion, physical training in patients with HF is associated with beneficial effects on natriuretic peptides and biomarkers of inflammation because they were all reduced by the intervention.
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The effect of lipoic acid on the content of SOD-1 and TNF-α in rat striated muscle. POSTEP HIG MED DOSW 2022. [DOI: 10.2478/ahem-2021-0051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
Background
The aim of the study was to present the effect of lipoic acid (LA) on oxidative stress induced by lipopolysaccharide (LPS).
Materials/Methods
The studies were conducted on male rats of the Wistar strain. The animals were divided into four groups. I: the controls received saline (0.2 ml); II: LPS, received LPS (Escherichia coli 026: B6) at a dose of 6 mg/kg body weight; III: LA, received LA at a dose of 60 mg/kg body weight; IV: LA + LPS, received LA (60 mg/kg b.w.) and after 30 min received LPS (6 mg/kg b.w.). All compounds were administered to the tail vein. After 5 hours of the experiment, the animals were anesthetized and striated muscle from the thigh was prepared. The isolated muscle was homogenized. Concentrations of superoxide dismutase-1 (SOD-1) and tumor necrosis factor alpha (TNF-α) were determined in the homogenates with the application of ELISA.
Results
The study showed a significant decrease in SOD-1 content and an increase in TNF-α in striated muscle after LPS administration. LA given 30 min before administration of LPS caused a significant increase in the level of SOD-1 and decreased levels of TNF-α in homogenates.
Conclusion
LA reduced the parameters of LPS oxidative stress, thus contributing to an increase in the body's antioxidant defense.
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Effects of Long-Term Regular Continuous and Intermittent Walking on Oxidative Stress, Metabolic Profile, Heart Rate Variability, and Blood Pressure in Older Adults with Hypertension. JOURNAL OF ENVIRONMENTAL AND PUBLIC HEALTH 2022; 2022:5942947. [PMID: 35140794 PMCID: PMC8820939 DOI: 10.1155/2022/5942947] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 01/04/2022] [Accepted: 01/18/2022] [Indexed: 12/14/2022]
Abstract
It is documented that regular exercise is beneficial for improving the antioxidant system, metabolic system, cardiac autonomic function, and blood pressure in those with hypertension. In this regard, low-intensity exercise is recommended for older adults, particularly those with chronic diseases. This study aimed to compare the effects of long-term regular continuous walking with intermittent walking on oxidative stress, metabolic profile, heart rate variability, and blood pressure in older adults with hypertension. Forty-three participants with hypertension aged 60–80 years were randomly divided into the continuous or intermittent walking (CON or INT) groups. Participants in the CON group walked for 30 min, 3 days/week for 12 weeks. Participants in the INT group split 30 min walking into 3 identical sessions punctuated by a 1 min rest after each session, 3 days/week for 12 weeks. Antioxidant and oxidative stress markers, metabolic markers, heart rate variability, and blood pressure were evaluated before and after the exercise program. Glutathione (GSH), GSH to GSH disulfide (GSSG) ratio, and total GSH increased significantly, and GSSG and malondialdehyde decreased significantly in both groups (
) without significant differences between groups. Triglycerides, ratio of total cholesterol to high-density lipoprotein cholesterol, and atherosclerogenic index were significantly lower in the CON group than those in the INT group (
). The standard deviation of the NN intervals and root mean square of the successive differences were significantly higher, and low-frequency power was significantly lower in the INT group than that in the CON group (
). No significant changes in blood pressure were noted in both groups, and nor were there any significant differences between groups. Long-term regular continuous and intermittent walking may comparably increase antioxidants, reduce oxidative stress, and be beneficial for improving important blood pressure-related outcomes, including metabolic profile or cardiac autonomic function in older adults with hypertension.
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Cunha RDDS, Costa GL, Pinto URC, Ferezin JJS, Cunha PHJD, Fioravanti MCS. Erythrogram and oxidative stress in confined cattle fed with Brachiaria sp hay and supplemented with antioxidants. CIÊNCIA ANIMAL BRASILEIRA 2022. [DOI: 10.1590/1809-6891v22e-70611e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Abstract Brachiaria sp contains sporidesmin that can be oxidized by lipoperoxidation and cause oxidative stress. In the present study we evaluated the effects of different antioxidants on lipoperoxidation of erythrocytes from Nelore cattle fed with Brachiaria sp hay. The experimental design was entirely randomized, in which 40 whole male cattle were divided into five treatments (G1: control - no supplementation; G2: selenium and vitamin E supplementation; G3: zinc supplementation; G4: selenium supplementation and G5: vitamin E supplementation) and allocated in feedlot pens for 105 days. The samples heparinized and withethylenediaminetetraacetic acid (EDTA) were obtained every 28 days for hematological and oxidative stress evaluation (0, 28 56, 84 and 105 days). In the erythrogram total erythrocyte count, hemoglobin, and hematocrit (Ht) were measured. For the evaluation of oxidative stress, in order to analyze the characteristics of the erythrocyte membrane, the thiobarbituric acid reactive substances (TBARS), total glutathione (GSH-T), glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) were determined. The results showed that regardless of the treatment there was no oxidative stress during the experimental confinement period and that the joint association of selenium and vitamin E in the bovine diet provided a lower incidence of deleterious alterations on erythrocytes.
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Cunha RDDS, Costa GL, Pinto URC, Ferezin JJS, Cunha PHJD, Fioravanti MCS. Eritrograma e estresse oxidativo em bovinos confinados alimentados com feno de Brachiaria sp. e suplementados com antioxidantes. CIÊNCIA ANIMAL BRASILEIRA 2022. [DOI: 10.1590/1809-6891v22e-70611p] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Resumo As Brachiaria sp contêm esporidesminas que podem ser oxidadas por lipoperoxidação e ocasionar estresse oxidativo. No presente estudo foram avaliados os efeitos de diferentes antioxidantes na lipoperoxidação dos eritrócitos de bovinos da raça Nelore, alimentados com feno de Brachiaria sp. O delineamento experimental foi inteiramente casualizado, em que 40 bovinos machos, inteiros, foram divididos, em cinco tratamentos (G1: controle - sem suplementação; G2: suplementação de selênio e vitamina E; G3: suplementação de zinco; G4: suplementação de selênio e G5: suplementação de vitamina E) e alocados em baias de confinamento, por 105 dias. As amostras de plasma heparinizado ou com ácido etilenodiamino tetra-acético (EDTA) foram obtidas a cada 28 dias para avaliação hematológica e de estresse oxidativo (0, 28 56, 84 e 105 dias). No eritrograma foi mensurado a contagem total de eritrócitos, a hemoglobina e o volume globular (VG). Para a avaliação do estresse oxidativo, com o objetivo de analisar as características da membrana do eritrócito foram determinadas as substâncias reativas ao ácido tiobarbitúrico (TBARS), glutationa total (GSH-T), glutationa peroxidase (GSH-Px), catalase (CAT) e superóxido dismutase (SOD). Os resultados demonstraram que independente do tratamento não houve estresse oxidativo durante o período do confinamento experimental e que a associação conjunta de selênio e vitamina E na dieta dos bovinos proporcionaram menor incidência de alterações deletérias sobre os eritrócitos.
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Giallauria F, Strisciuglio T, Cuomo G, Di Lorenzo A, D'Angelo A, Volpicelli M, Izzo R, Manzi MV, Barbato E, Morisco C. Exercise Training: The Holistic Approach in Cardiovascular Prevention. High Blood Press Cardiovasc Prev 2021; 28:561-577. [PMID: 34724167 PMCID: PMC8590648 DOI: 10.1007/s40292-021-00482-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 10/23/2021] [Indexed: 12/26/2022] Open
Abstract
Nowadays, there are robust clinical and pathophysiological evidence supporting the beneficial effects of physical activity on cardiovascular (CV) system. Thus, the physical activity is considered a key strategy for CV prevention. In fact, exercise training exerts favourable effects on all risk factors for CV diseases (i.e. essential hypertension, type 2 diabetes mellitus, hypercholesterolemia, obesity, metabolic syndrome, etc…). In addition, all training modalities such as the aerobic (continuous walking, jogging, cycling, etc.) or resistance exercise (weights), as well as the leisure-time physical activity (recreational walking, gardening, etc) prevent the development of the major CV risk factors, or delay the progression of target organ damage improving cardio-metabolic risk. Exercise training is also the core component of all cardiac rehabilitation programs that have demonstrated to improve the quality of life and to reduce morbidity in patients with CV diseases, mostly in patients with coronary artery diseases. Finally, it is still debated whether or not exercise training can influence the occurrence of atrial and ventricular arrhythmias. In this regard, there is some evidence that exercise training is protective predominantly for atrial arrhythmias, reducing the incidence of atrial fibrillation. In conclusion, the salutary effects evoked by physical acitvity are useful in primary and secondary CV prevention.
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Affiliation(s)
- Francesco Giallauria
- Department of Translational Medical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Teresa Strisciuglio
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Gianluigi Cuomo
- Department of Translational Medical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Anna Di Lorenzo
- Department of Translational Medical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Andrea D'Angelo
- Department of Translational Medical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Mario Volpicelli
- Department of Cardiology, "Santa Maria della Pietà" Hospital (ASL Napoli 3 Sud), 80035, Nola, NA, Italy
| | - Raffaele Izzo
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Maria Virginia Manzi
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Emanuele Barbato
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples, 80131, Naples, Italy
| | - Carmine Morisco
- Department of Advanced Biomedical Sciences, "Federico II" University of Naples, 80131, Naples, Italy.
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Lu Z, Xu Y, Song Y, Bíró I, Gu Y. A Mixed Comparisons of Different Intensities and Types of Physical Exercise in Patients With Diseases Related to Oxidative Stress: A Systematic Review and Network Meta-Analysis. Front Physiol 2021; 12:700055. [PMID: 34421637 PMCID: PMC8375596 DOI: 10.3389/fphys.2021.700055] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Accepted: 06/16/2021] [Indexed: 12/25/2022] Open
Abstract
The balance of oxidative and antioxidant systems is of great importance to the human body. Physical exercise, as one of the ways to improve physical health, seems to modulate this balance. However, different intensities and types of physical exercise have other effects on the treatment of unhealthy people. To understand the impact of exercise training on the oxidative and antioxidant systems of adults with oxidative stress-related disorders, a network meta-analysis was used to compare the mixed effects of different intensities and types of exercise training. This systematic review included all eligible RCTs from PubMed, Medline, Cochrane Library, and CINAHL. Eleven of the studies met the inclusion criteria (at study completion, n = 666 participants). Seven studies reported that the level of MDA decreased significantly after exercise (p < 0.05), and 3 studies reported that the level of SOD increased significantly after exercise (p < 0.05). In conclusion, long-term high-intensity aerobic training and Tai Chi or Yoga can effectively improve oxidative stress in unhealthy people. In addition, different types of diseases on the effect of exercise intervention seems to be other, diabetes and chronic kidney patients using moderate-intensity aerobic training or Tai chi and Yoga effect are better; Moderate-intensity aerobic training had a better impact on OS improvement in patients with irritable bowel syndrome and severe depression. However, more research is needed to determine the effects of different levels and types of physical activity on oxidative stress in unhealthy populations. Systematic Review Registration: PROSPERO identifier: CRD42021242025. https://www.crd.york.ac.uk/prospero/.
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Affiliation(s)
- Zhenghui Lu
- Faculty of Sports Science, Ningbo University, Ningbo, China
| | - Yining Xu
- Faculty of Sports Science, Ningbo University, Ningbo, China
| | - Yang Song
- Faculty of Sports Science, Ningbo University, Ningbo, China.,Doctoral School on Safety and Security Sciences, Obuda University, Budapest, Hungary.,Faculty of Engineering, University of Szeged, Szeged, Hungary
| | - István Bíró
- Faculty of Engineering, University of Szeged, Szeged, Hungary
| | - Yaodong Gu
- Faculty of Sports Science, Ningbo University, Ningbo, China
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35
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Jaconiano E, Moreira-Gonçalves D. Unveiling the role of exercise training in targeting the inflammatory paradigm of heart failure with preserved ejection fraction: a narrative review. Heart Fail Rev 2021; 27:163-190. [PMID: 34244870 DOI: 10.1007/s10741-021-10138-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/01/2021] [Indexed: 12/30/2022]
Abstract
Heart failure with preserved ejection fraction (HFpEF) is currently lacking an effective pharmacological treatment with impact on major outcomes such as hospitalization and mortality. Exercise training (EXT) is recognized as an important nonpharmacological tool, capable of improving exercise capacity and quality of life, and has even been associated with a reduction in hospitalization and cardiovascular mortality risk. However, this positive impact largely lacks a physiological explanation. The aim of this narrative review was to provide an overview of the available data supporting the hypothesis that the beneficial role of EXT in HFpEF might be due to its effects on targeting the inflammatory paradigm described for this disease. A comprehensive literature search was conducted using the PubMed-NCBI database. We reviewed the effects of EXT throughout each step of the pathophysiological pathway leading to HFpEF and found clinical and/or preclinical evidence supporting the reduction of systemic inflammation, endothelial dysfunction, microvascular rarefaction, and myocardial stiffness. We also highlighted some gaps in the knowledge or topics that deserve further clarification in future studies. In conclusion, despite the scarcity of clinical studies in this population, there is compelling evidence suggesting that EXT modulates crucial aspects of the inflammatory pathway described for HFpEF and future investigation on cellular and molecular mechanisms are encouraged.
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Affiliation(s)
- Eliane Jaconiano
- Cardiovascular R&D Center (UnIC) and Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
| | - Daniel Moreira-Gonçalves
- Centre of Physical Activity, Health and Leisure (CIAFEL), Faculty of Sport, University of Porto, Porto, Portugal
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36
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Harwood AE, Russell S, Okwose NC, McGuire S, Jakovljevic DG, McGregor G. A systematic review of rehabilitation in chronic heart failure: evaluating the reporting of exercise interventions. ESC Heart Fail 2021; 8:3458-3471. [PMID: 34235878 PMCID: PMC8497377 DOI: 10.1002/ehf2.13498] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 05/17/2021] [Accepted: 06/16/2021] [Indexed: 12/13/2022] Open
Abstract
A large body of research supports the use of exercise to improve symptoms, quality of life, and physical function in patients with chronic heart failure. Previous reviews have focused on reporting outcomes of exercise interventions such as cardiorespiratory fitness. However, none have critically examined exercise prescription. The aim of this review was to evaluate the reporting and application of exercise principles in randomised control trials of exercise training in patients with chronic heart failure. A systematic review of exercise intervention RCTs in patients with CHF, using the Consensus on Exercise Reporting Template (CERT), was undertaken. The Ovid Medline/PubMed, Embase, Scopus/Web of Science, and Cochrane Library and Health Technology Assessment Databases were searched from 2000 to June 2020. Prospective RCTs in which patients with CHF were randomized to a structured exercise programme were included. No limits were placed on the type or duration of exercise structured exercise programme or type of CHF (i.e. preserved or reduced ejection fraction). We included 143 studies, comprising of 181 different exercise interventions. The mean CERT score was 10 out of 19, with no study achieving a score of 19. Primarily, details were missing regarding motivational strategies, home-based exercise components, and adherence/fidelity to the intervention. Exercise intensity was the most common principle of exercise prescription missing from intervention reporting. There was no improvement in the reporting of exercise interventions with time (R2 = 0.003). Most RCTs of exercise training in CHF are reported with insufficient detail to allow for replication, limiting the translation of evidence to clinical practice. We encourage authors to provide adequate details when reporting future interventions. Where journal word counts are restrictive, we recommend using supplementary material or publishing trial protocols prior to beginning the study.
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Affiliation(s)
- Amy E Harwood
- Centre for Sport, Exercise and Life Sciences, Faculty of Health and Life Sciences, Science and Health Building, Whitefriars Street, Coventry University, Coventry, CV1 2DS, UK
| | - Sophie Russell
- Centre for Sport, Exercise and Life Sciences, Faculty of Health and Life Sciences, Science and Health Building, Whitefriars Street, Coventry University, Coventry, CV1 2DS, UK
| | - Nduka C Okwose
- Centre for Sport, Exercise and Life Sciences, Faculty of Health and Life Sciences, Science and Health Building, Whitefriars Street, Coventry University, Coventry, CV1 2DS, UK.,Cardiovascular Research Division, Translational and Clinical Research Institute, Newcastle University, UK
| | - Scott McGuire
- Centre for Sport, Exercise and Life Sciences, Faculty of Health and Life Sciences, Science and Health Building, Whitefriars Street, Coventry University, Coventry, CV1 2DS, UK
| | - Djordje G Jakovljevic
- Centre for Sport, Exercise and Life Sciences, Faculty of Health and Life Sciences, Science and Health Building, Whitefriars Street, Coventry University, Coventry, CV1 2DS, UK.,Cardiovascular Research Division, Translational and Clinical Research Institute, Newcastle University, UK.,Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Gordon McGregor
- Centre for Sport, Exercise and Life Sciences, Faculty of Health and Life Sciences, Science and Health Building, Whitefriars Street, Coventry University, Coventry, CV1 2DS, UK.,Department of Cardiopulmonary Rehabilitation, Centre for Exercise and Health, University Hospitals Coventry & Warwickshire NHS Trust, Coventry, UK
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Al-Mubarak AA, van der Meer P, Bomer N. Selenium, Selenoproteins, and Heart Failure: Current Knowledge and Future Perspective. Curr Heart Fail Rep 2021; 18:122-131. [PMID: 33835398 PMCID: PMC8163712 DOI: 10.1007/s11897-021-00511-4] [Citation(s) in RCA: 59] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/22/2021] [Indexed: 12/18/2022]
Abstract
PURPOSE OF REVIEW (Mal-)nutrition of micronutrients, like selenium, has great impact on the human heart and improper micronutrient intake was observed in 30-50% of patients with heart failure. Low selenium levels have been reported in Europe and Asia and thought to be causal for Keshan disease. Selenium is an essential micronutrient that is needed for enzymatic activity of the 25 so-called selenoproteins, which have a broad range of activities. In this review, we aim to summarize the current evidence about selenium in heart failure and to provide insights about the potential mechanisms that can be modulated by selenoproteins. RECENT FINDINGS Suboptimal selenium levels (<100 μg/L) are prevalent in more than 70% of patients with heart failure and were associated with lower exercise capacity, lower quality of life, and worse prognosis. Small clinical trials assessing selenium supplementation in patients with HF showed improvement of clinical symptoms (NYHA class), left ventricular ejection fraction, and lipid profile, while governmental interventional programs in endemic areas have significantly decreased the incidence of Keshan disease. In addition, several selenoproteins are found impaired in suboptimal selenium conditions, potentially aggravating underlying mechanisms like oxidative stress, inflammation, and thyroid hormone insufficiency. While the current evidence is not sufficient to advocate selenium supplementation in patients with heart failure, there is a clear need for high level evidence to show whether treatment with selenium has a place in the contemporary treatment of patients with HF to improve meaningful clinical endpoints. Graphical summary summarizing the potential beneficial effects of the various selenoproteins, locally in cardiac tissues and systemically in the rest of the body. In short, several selenoproteins contribute in protecting the integrity of the mitochondria. By doing so, they contribute indirectly to reducing the oxidative stress as well as improving the functionality of immune cells, which are in particular vulnerable to oxidative stress. Several other selenoproteins are directly involved in antioxidative pathways, next to excreting anti-inflammatory effects. Similarly, some selenoproteins are located in the endoplasmic reticulum, playing roles in protein folding. With exception of the protection of the mitochondria and the reduction of oxidative stress, other effects are not yet investigated in cardiac tissues. The systemic effects of selenoproteins might not be limited to these mechanisms, but also may include modulation of endothelial function, protection skeletal muscles, in addition to thyroid metabolism. ABBREVIATIONS DIO, iodothyronine deiodinase; GPx, glutathione peroxidase; MsrB2, methionine-R-sulfoxide reductase B2; SELENOK, selenoprotein K; SELENON, selenoprotein N; SELENOP, selenoprotein P; SELENOS, selenoprotein S; SELENOT, selenoprotein T; TXNRD, thioredoxin reductase.
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Affiliation(s)
- Ali A Al-Mubarak
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Peter van der Meer
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Nils Bomer
- Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
- Department of Experimental Cardiology, University Medical Center Groningen, UMCG Post-zone AB43, P.O. Box 30.001, 9700, RB, Groningen, The Netherlands.
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Jamka M, Bogdański P, Krzyżanowska-Jankowska P, Miśkiewicz-Chotnicka A, Karolkiewicz J, Duś-Żuchowska M, Mądry R, Lisowska A, Gotz-Więckowska A, Iskakova S, Walkowiak J, Mądry E. Endurance Training Depletes Antioxidant System but Does Not Affect Endothelial Functions in Women with Abdominal Obesity: A Randomized Trial with a Comparison to Endurance-Strength Training. J Clin Med 2021; 10:1639. [PMID: 33921520 PMCID: PMC8068807 DOI: 10.3390/jcm10081639] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 04/06/2021] [Accepted: 04/09/2021] [Indexed: 01/02/2023] Open
Abstract
Limited data suggested that inclusion of a strength component into endurance exercises might intensify the beneficial effect of training. However, the available data is limited. Therefore, we aimed to compare the effect of endurance and endurance-strength training on anthropometric parameters, endothelial function, arterial stiffness, antioxidant status, and inflammatory markers in abdominally obese women without serious comorbidities. A total of 101 women were recruited and randomly divided into endurance (n = 52) and endurance-strength (n = 49) groups. During the three-month intervention, both groups performed supervised sixty-minute training three times a week. All studied parameters were measured pre- and post-intervention period. In total, 85 women completed the study. Both training significantly decreased anthropometric parameters. Besides, endurance training decreased endothelial nitric oxide synthase, central aortic systolic pressure, pulse wave velocity, glutathione (GSH), total antioxidant status (TAS), interleukin (IL) 8, matrix metalloproteinase (MMP) 9, and tumor necrosis factor alpha, while endurance-strength training decreased MMP-2 concentrations, and increased IL-6, monocyte chemoattractant protein-1, and MMP-9 levels. We observed significant differences between groups for GSH, TAS, and MMP-9 levels. In summary, endurance and endurance-strength training did not differ in the impact on endothelial function and arterial stiffness. However, endurance training significantly depleted the antioxidant defense, simultaneously reducing MMP-9 levels. The study was retrospectively registered with the German Clinical Trials Register within the number DRKS00019832.
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Affiliation(s)
- Małgorzata Jamka
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna Str. 27/33, 60-572 Poznań, Poland; (M.J.); (P.K.-J.); (A.M.-C.); (M.D.-Ż.)
| | - Paweł Bogdański
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, Szamarzewskiego Str. 82, 60-569 Poznań, Poland;
| | - Patrycja Krzyżanowska-Jankowska
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna Str. 27/33, 60-572 Poznań, Poland; (M.J.); (P.K.-J.); (A.M.-C.); (M.D.-Ż.)
| | - Anna Miśkiewicz-Chotnicka
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna Str. 27/33, 60-572 Poznań, Poland; (M.J.); (P.K.-J.); (A.M.-C.); (M.D.-Ż.)
| | - Joanna Karolkiewicz
- Department of Food and Nutrition, Poznan University of Physical Education, Królowej Jadwigi Str. 27/39, 61-871 Poznań, Poland;
| | - Monika Duś-Żuchowska
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna Str. 27/33, 60-572 Poznań, Poland; (M.J.); (P.K.-J.); (A.M.-C.); (M.D.-Ż.)
| | - Radosław Mądry
- Department of Oncology, Poznan University of Medical Sciences, Szamarzewskiego Str. 84, 60-569 Poznań, Poland;
| | - Aleksandra Lisowska
- Department of Clinical Auxology and Pediatric Nursing, Poznan University of Medical Sciences, Szpitalna Str. 27/33, 60-572 Poznań, Poland;
| | - Anna Gotz-Więckowska
- Department of Ophthalmology, Poznan University of Medical Sciences, Szamarzewskiego Str. 84, 60-569 Poznań, Poland;
| | - Saule Iskakova
- Department of Pharmacology, Asfendiyarov Kazakh National Medical University, Tole Bi Str. 94, Almaty 050000, Kazakhstan;
| | - Jarosław Walkowiak
- Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Szpitalna Str. 27/33, 60-572 Poznań, Poland; (M.J.); (P.K.-J.); (A.M.-C.); (M.D.-Ż.)
| | - Edyta Mądry
- Department of Physiology, Poznan University of Medical Sciences, Święcickiego Str. 6, 60-781 Poznań, Poland;
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Rentz T, Wanschel ACBA, de Carvalho Moi L, Lorza-Gil E, de Souza JC, Dos Santos RR, Oliveira HCF. The Anti-atherogenic Role of Exercise Is Associated With the Attenuation of Bone Marrow-Derived Macrophage Activation and Migration in Hypercholesterolemic Mice. Front Physiol 2020; 11:599379. [PMID: 33329050 PMCID: PMC7719785 DOI: 10.3389/fphys.2020.599379] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 11/03/2020] [Indexed: 12/13/2022] Open
Abstract
An early event in atherogenesis is the recruitment and infiltration of circulating monocytes and macrophage activation in the subendothelial space. Atherosclerosis subsequently progresses as a unresolved inflammatory disease, particularly in hypercholesterolemic conditions. Although physical exercise training has been a widely accepted strategy to inhibit atherosclerosis, its impact on arterial wall inflammation and macrophage phenotype and function has not yet been directly evaluated. Thus, the aim of this study was to investigate the effects of aerobic exercise training on the inflammatory state of atherosclerotic lesions with a focus on macrophages. Hypercholesterolemic LDL-receptor-deficient male mice were subjected to treadmill training for 8 weeks and fed a high-fat diet. Analyses included plasma lipoprotein and cytokine levels; aortic root staining for lipids (oil red O); macrophages (CD68, MCP1 and IL1β); oxidative (nitrotyrosine and, DHE) and endoplasmic reticulum (GADD) stress markers. Primary bone marrow-derived macrophages (BMDM) were assayed for migration activity, motility phenotype (Rac1 and F-actin) and inflammation-related gene expression. Plasma levels of HDL cholesterol were increased, while levels of proinflammatory cytokines (TNFa, IL1b, and IL6) were markedly reduced in the exercised mice. The exercised mice developed lower levels of lipid content and inflammation in atherosclerotic plaques. Additionally, lesions in the exercised mice had lower levels of oxidative and ER stress markers. BMDM isolated from the exercised mice showed a marked reduction in proinflammatory cytokine gene expression and migratory activity and a disrupted motility phenotype. More importantly, bone marrow from exercised mice transplanted into sedentary mice led to reduced atherosclerosis in the recipient sedentary mice, thus suggesting that epigenetic mechanisms are associated with exercise. Collectively, the presented data indicate that exercise training prevents atherosclerosis by inhibiting bone marrow-derived macrophage recruitment and activation.
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Affiliation(s)
- Thiago Rentz
- Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Brazil
| | - Amarylis C B A Wanschel
- Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Brazil
| | - Leonardo de Carvalho Moi
- Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Brazil
| | - Estela Lorza-Gil
- Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Brazil
| | - Jane C de Souza
- Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Brazil
| | - Renata R Dos Santos
- Division of Radiotherapy, Faculty of Medical Sciences, Medical School Hospital, State University of Campinas, Campinas, Brazil
| | - Helena C F Oliveira
- Department of Structural and Functional Biology, Institute of Biology, State University of Campinas, Campinas, Brazil
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Goto K, Schauer A, Augstein A, Methawasin M, Granzier H, Halle M, Craenenbroeck EMV, Rolim N, Gielen S, Pieske B, Winzer EB, Linke A, Adams V. Muscular changes in animal models of heart failure with preserved ejection fraction: what comes closest to the patient? ESC Heart Fail 2020; 8:139-150. [PMID: 33350094 PMCID: PMC7835579 DOI: 10.1002/ehf2.13142] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 10/31/2020] [Accepted: 11/15/2020] [Indexed: 12/16/2022] Open
Abstract
AIMS Heart failure with preserved ejection fraction (HFpEF) is associated with reduced exercise capacity elicited by skeletal muscle (SM) alterations. Up to now, no clear medical treatment advice for HFpEF is available. Identification of the ideal animal model mimicking the human condition is a critical step in developing and testing treatment strategies. Several HFpEF animals have been described, but the most suitable in terms of comparability with SM alterations in HFpEF patients is unclear. The aim of the present study was to investigate molecular changes in SM of three different animal models and to compare them with alterations of muscle biopsies obtained from human HFpEF patients. METHODS AND RESULTS Skeletal muscle tissue was obtained from HFpEF and control patients and from three different animal models including the respective controls-ZSF1 rat, Dahl salt-sensitive rat, and transverse aortic constriction surgery/deoxycorticosterone mouse. The development of HFpEF was verified by echocardiography. Protein expression and enzyme activity of selected markers were assessed in SM tissue homogenates. Protein expression between SM tissue obtained from HFpEF patients and the ZSF1 rats revealed similarities for protein markers involved in muscle atrophy (MuRF1 expression, protein ubiquitinylation, and LC3) and mitochondrial metabolism (succinate dehydrogenase and malate dehydrogenase activity, porin expression). The other two animal models exhibited far less similarities to the human samples. CONCLUSIONS None of the three tested animal models mimics the condition in HFpEF patients completely, but among the animal models tested, the ZSF1 rat (ZSF1-lean vs. ZSF1-obese) shows the highest overlap to the human condition. Therefore, when studying therapeutic interventions to treat HFpEF and especially alterations in the SM, we suggest that the ZSF1 rat is a suitable model.
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Affiliation(s)
- Keita Goto
- Laboratory for Experimental and Molecular Cardiology, Department of Internal Medicine and Cardiology, TU Dresden, Heart Center Dresden University Hospital, Fetscherstrasse 76, Dresden, 01307, Germany
| | - Antje Schauer
- Laboratory for Experimental and Molecular Cardiology, Department of Internal Medicine and Cardiology, TU Dresden, Heart Center Dresden University Hospital, Fetscherstrasse 76, Dresden, 01307, Germany
| | - Antje Augstein
- Laboratory for Experimental and Molecular Cardiology, Department of Internal Medicine and Cardiology, TU Dresden, Heart Center Dresden University Hospital, Fetscherstrasse 76, Dresden, 01307, Germany
| | - Mei Methawasin
- Department of Cellular and Molecular Medicine, University of Arizona, Tucson, USA
| | - Henk Granzier
- Department of Cellular and Molecular Medicine, University of Arizona, Tucson, USA
| | - Martin Halle
- Prevention and Sports Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.,DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
| | | | - Natale Rolim
- Department of Circulation and Medical Imaging, Faculty of Medicine, NTNU, K.G. Jebsen Center of Exercise in Medicine, Trondheim, Norway
| | - Stephan Gielen
- Department of Cardiology, Angiology and Intensive Care, Klinikum Lippe, Detmold, Germany
| | - Burkert Pieske
- Department of Internal Medicine and Cardiology Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Ephraim B Winzer
- Laboratory for Experimental and Molecular Cardiology, Department of Internal Medicine and Cardiology, TU Dresden, Heart Center Dresden University Hospital, Fetscherstrasse 76, Dresden, 01307, Germany
| | - Axel Linke
- Laboratory for Experimental and Molecular Cardiology, Department of Internal Medicine and Cardiology, TU Dresden, Heart Center Dresden University Hospital, Fetscherstrasse 76, Dresden, 01307, Germany.,Dresden Cardiovascular Research Institute and Core Laboratories GmbH, Dresden, Germany
| | - Volker Adams
- Laboratory for Experimental and Molecular Cardiology, Department of Internal Medicine and Cardiology, TU Dresden, Heart Center Dresden University Hospital, Fetscherstrasse 76, Dresden, 01307, Germany.,Dresden Cardiovascular Research Institute and Core Laboratories GmbH, Dresden, Germany
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Knapp F, Niemann B, Li L, Molenda N, Kracht M, Schulz R, Rohrbach S. Differential effects of right and left heart failure on skeletal muscle in rats. J Cachexia Sarcopenia Muscle 2020; 11:1830-1849. [PMID: 32985798 PMCID: PMC7749622 DOI: 10.1002/jcsm.12612] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 05/17/2020] [Accepted: 07/07/2020] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Exercise intolerance is a cardinal symptom in right (RV) and left ventricular (LV) failure. The underlying skeletal muscle contributes to increased morbidity in patients. Here, we compared skeletal muscle sarcopenia in a novel two-stage model of RV failure to an established model of LV failure. METHODS Pulmonary artery banding (PAB) or aortic banding (AOB) was performed in weanling rats, inducing a transition from compensated cardiac hypertrophy (after 7 weeks) to heart failure (after 22-26 weeks). Cardiac function was characterized by echocardiography. Skeletal muscle catabolic/anabolic balance and energy metabolism were analysed by histological and biochemical methods, real-time PCR, and western blot. RESULTS Two clearly distinguishable stages of left or right heart disease with a comparable severity were reached. However, skeletal muscle impairment was significantly more pronounced in LV failure. While the compensatory stage resulted only in minor changes, soleus and gastrocnemius muscle of AOB rats at the decompensated stage demonstrated reduced weight and fibre diameter, higher proteasome activity and expression of the muscle-specific ubiquitin E3 ligases muscle-specific RING finger 1 and atrogin-1, increased expression of the atrophy marker myostatin, increased autophagy activation, and impaired mitochondrial function and respiratory chain gene expression. Soleus and gastrocnemius muscle of PAB rats did not show significant changes in muscle weight and proteasome or autophagy activation, but mitochondrial function was mildly impaired as well. The diaphragm did not demonstrate differences in any model or disease stage except for myostatin expression, which was altered at the decompensated stage in both models. Plasma interleukin (IL)-6 and angiotensin II were strongly increased at the decompensated stage (AOB > > PAB). Soleus and gastrocnemius muscle itself demonstrated an increase in IL-6 expression independent from blood-derived cytokines only in AOB animals. In vitro experiments in rat skeletal muscle cells suggested a direct impact of IL-6 and angiotensin II on distinctive atrophic changes. CONCLUSIONS Manifold skeletal muscle alterations are more pronounced in LV failure compared with RV failure despite a similar ventricular impairment. Most of the catabolic changes were observed in soleus or gastrocnemius muscle rather than in the constantly active diaphragm. Mitochondrial dysfunction and up-regulation of myostatin were identified as the earliest signs of skeletal muscle impairment.
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Affiliation(s)
- Fabienne Knapp
- Institute of Physiology, Justus Liebig University Giessen, Giessen, Germany
| | - Bernd Niemann
- Department of Adult and Pediatric Cardiac and Vascular Surgery, University Hospital Giessen and Marburg, Justus Liebig University Giessen, Rudolf-Buchheim-Strasse 7, Giessen, 35392, Germany
| | - Ling Li
- Institute of Physiology, Justus Liebig University Giessen, Giessen, Germany
| | - Nicole Molenda
- Institute of Physiology, Justus Liebig University Giessen, Giessen, Germany
| | - Michael Kracht
- Rudolf Buchheim Institute of Pharmacology, Justus Liebig University Giessen, Schubertstrasse 81, Giessen, 35392, Germany
| | - Rainer Schulz
- Institute of Physiology, Justus Liebig University Giessen, Giessen, Germany
| | - Susanne Rohrbach
- Institute of Physiology, Justus Liebig University Giessen, Giessen, Germany
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Carbone S, Billingsley HE, Rodriguez-Miguelez P, Kirkman DL, Garten R, Franco RL, Lee DC, Lavie CJ. Lean Mass Abnormalities in Heart Failure: The Role of Sarcopenia, Sarcopenic Obesity, and Cachexia. Curr Probl Cardiol 2020; 45:100417. [PMID: 31036371 PMCID: PMC11146283 DOI: 10.1016/j.cpcardiol.2019.03.006] [Citation(s) in RCA: 98] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Accepted: 03/24/2019] [Indexed: 02/07/2023]
Abstract
The role of body composition in patients with heart failure (HF) has been receiving much attention in the last few years. Particularly, reduced lean mass (LM), the best surrogate for skeletal muscle mass, is independently associated with abnormal cardiorespiratory fitness (CRF) and muscle strength, ultimately leading to reduced quality of life and worse prognosis. While in the past, reduced CRF in patients with HF was thought to result exclusively from cardiac dysfunction leading to reduced cardiac output at peak exercise, current evidence supports the concept that abnormalities in LM may also play a critical role. Abnormalities in the LM body composition compartment are associated with the development of sarcopenia, sarcopenic obesity, and cachexia. Such conditions have been implicated in the pathophysiology and progression of HF. However, identification of such conditions remains challenging, as universal definitions for sarcopenia, sarcopenic obesity, and cachexia are lacking. In this review article, we describe the most common body composition abnormalities related to the LM compartment, including skeletal and respiratory muscle mass abnormalities, and the consequences of such anomalies on CRF and muscle strength in patients with HF. Finally, we discuss the potential nonpharmacologic therapeutic strategies such as exercise training (ie, aerobic exercise and resistance exercise) and dietary interventions (ie, dietary supplementation and dietary patterns) that have been implemented to target body composition, with a focus on HF.
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Saidu Y, Olaosebikan RO, Isa SA, Malami I, Muhammad SA. Effect of natron administration on the antioxidant status and lipid profile of rats. J Food Sci 2020; 85:4033-4038. [PMID: 33000512 DOI: 10.1111/1750-3841.15480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 08/31/2020] [Accepted: 09/08/2020] [Indexed: 11/30/2022]
Abstract
Natron consumption has been implicated in the pathogenesis of peripartum cardiomyopathy. This work evaluates the effect of natron on the antioxidant status and lipid profile of postpartum rats administered graded doses of natron for four consecutive weeks. After treatment, the rats were assessed for antioxidant status, malondialdehyde level, and lipid profile. The results revealed that natron caused a significant decrease (P ˂ 0.05) in the activity of catalase in rats administered with 300 mg/kg of natron compared to control. The activities of superoxide dismutase and glutathione peroxidase decreased in a dose-dependent manner; however, the difference was not statistically significant when compared with control. Serum levels of antioxidant minerals were also significantly decreased (P ˂ 0.05) at higher doses of natron in comparison to control. There was a significant increase (P < 0.05) in the malondialdehyde level in rats administered with 200 and 300 mg/kg of natron when compared with control. Natron at higher doses caused a significant increase (P ˂ 0.05) in the level of the lipid profile parameters except for high-density lipoprotein-cholesterol that decrease significantly (P ˂ 0.05). This study demonstrated that the administration of natron at high doses induced dyslipidemia and oxidative stress in postpartum rats. PRACTICAL APPLICATION: This research reports the implication of a high intake of natron to health and to establish the relationship between natron intake and peripartum cardiomyopathy (PPCM) using an animal model. Natron has health benefits; however, its consumption at high doses should be discouraged as it can lead to oxidative stress (OS) and dyslipidemia. The results suggest that OS due to natron may contribute to the pathogenesis of PPCM. A high concentration of natron can be used to induce an animal model of PPCM, which would be of practical application in studying the molecular basis and possible discovery of therapeutics for the disease.
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Affiliation(s)
- Yusuf Saidu
- Department of Biochemistry, Usmanu Danfodiyo University, Sokoto, Nigeria
| | | | - Suleiman Ahmed Isa
- Department of Biochemistry, Usmanu Danfodiyo University, Sokoto, Nigeria
| | - Ibrahim Malami
- Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria
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Immunomodulator Drug (IMODTM) and Exercise Improve Cardiac Oxidative Stress and Antioxidant Balance in Diabetic Rats. Jundishapur J Nat Pharm Prod 2020. [DOI: 10.5812/jjnpp.62898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
: Diabetes is a common metabolic disease that increases the risk of cardiovascular disease. It seems that the reduction of oxidative stress or increasing antioxidant levels improves diabetic cardiomyopathy. Antioxidant effects of immunomodulatory drug (IMODTM) and also beneficial influences of exercise on diabetic complications have been shown. The present study examined the effects of IMODTM and exercise on cardiac oxidative stress and antioxidants in diabetes. For this purpose, 64 rats were divided into 8 groups: control (C), exercise (E), IMODTM (20 mg/kg) (I), exercise plus IMODTM (E + I), diabetes (D), diabetic rats treated with exercise (D + E), diabetic rats treated with IMODTM (D + I), and diabetic rats treated with exercise plus IMODTM (D + E + I). Treatments with exercise and/or IMODTM were performed for 8 weeks. Type 1 diabetes was induced by intraperitoneal injection of 60 mg/kg streptozotocin. After the treatment period, all rats were anesthetized, and blood and heart samples were gathered for measurement of malondialdehyde (MDA) as an oxidative stress marker, lactate dehydrogenase (LDH) as a cardiac injury marker, total antioxidant capacity (TAC), and superoxide dismutase (SOD) as well as glutathione peroxidase (GPx) as antioxidant enzymes. The present study, for the first time, showed that IMODTM alone or in combination with exercise had positive effects on alleviating hyperglycemia, MDA, and LDH along with elevation of antioxidant enzymes activities in type 1 diabetic rats.
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Tekos F, Skaperda Z, Goutzourelas N, Phelps DS, Floros J, Kouretas D. The Importance of Redox Status in the Frame of Lifestyle Approaches and the Genetics of the Lung Innate Immune Molecules, SP-A1 and SP-A2, on Differential Outcomes of COVID-19 Infection. Antioxidants (Basel) 2020; 9:antiox9090784. [PMID: 32854247 PMCID: PMC7554878 DOI: 10.3390/antiox9090784] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 08/20/2020] [Accepted: 08/21/2020] [Indexed: 02/07/2023] Open
Abstract
The pandemic of COVID-19 is of great concern to the scientific community. This mainly affects the elderly and people with underlying diseases. People with obesity are more likely to experience unpleasant disease symptoms and increased mortality. The severe oxidative environment that occurs in obesity due to chronic inflammation permits viral activation of further inflammation leading to severe lung disease. Lifestyle affects the levels of inflammation and oxidative stress. It has been shown that a careful diet rich in antioxidants, regular exercise, and fasting regimens, each and/or together, can reduce the levels of inflammation and oxidative stress and strengthen the immune system as they lead to weight loss and activate cellular antioxidant mechanisms and reduce oxidative damage. Thus, a lifestyle change based on the three pillars: antioxidants, exercise, and fasting could act as a proactive preventative measure against the adverse effects of COVID-19 by maintaining redox balance and well-functioning immunity. Moreover, because of the observed diversity in the expression of COVID-19 inflammation, the role of genetics of innate immune molecules, surfactant protein A (SP-A)1 and SP-A2, and their differential impact on the local lung microenvironment and host defense is reviewed as genetics may play a major role in the diverse expression of the disease.
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Affiliation(s)
- Fotios Tekos
- Department of Biochemistry-Biotechnology, University of Thessaly, 41500 Larissa, Greece; (F.T.); (Z.S.); (N.G.)
| | - Zoi Skaperda
- Department of Biochemistry-Biotechnology, University of Thessaly, 41500 Larissa, Greece; (F.T.); (Z.S.); (N.G.)
| | - Nikolaos Goutzourelas
- Department of Biochemistry-Biotechnology, University of Thessaly, 41500 Larissa, Greece; (F.T.); (Z.S.); (N.G.)
| | - David S. Phelps
- Center for Host Defense, Inflammation, and Lung Disease (CHILD) and Departments of Pediatrics, Hershey, PA 17033, USA; (D.S.P.); (J.F.)
| | - Joanna Floros
- Center for Host Defense, Inflammation, and Lung Disease (CHILD) and Departments of Pediatrics, Hershey, PA 17033, USA; (D.S.P.); (J.F.)
- Obstetrics & Gynecology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
| | - Demetrios Kouretas
- Department of Biochemistry-Biotechnology, University of Thessaly, 41500 Larissa, Greece; (F.T.); (Z.S.); (N.G.)
- Correspondence: ; Tel.: +30-2410-565-277; Fax: +30-2410-565-290
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Bardi E, Majerczak J, Zoladz JA, Tyrankiewicz U, Skorka T, Chlopicki S, Jablonska M, Bar A, Jasinski K, Buso A, Salvadego D, Nieckarz Z, Grassi B, Bottinelli R, Pellegrino MA. Voluntary physical activity counteracts Chronic Heart Failure progression affecting both cardiac function and skeletal muscle in the transgenic Tgαq*44 mouse model. Physiol Rep 2020; 7:e14161. [PMID: 31267722 PMCID: PMC6606516 DOI: 10.14814/phy2.14161] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Accepted: 06/11/2019] [Indexed: 12/20/2022] Open
Abstract
Physical activity is emerging as an alternative nonpharmaceutical strategy to prevent and treat a variety of cardiovascular diseases due to its cardiac and skeletal muscle beneficial effects. Oxidative stress occurs in skeletal muscle of chronic heart failure (CHF) patients with possible impact on muscle function decline. We determined the effect of voluntary‐free wheel running (VFWR) in preventing protein damage in Tgαq*44 transgenic mice (Tg) characterized by a delayed CHF progression. In the early (6 months) and transition (12 months) phase of CHF, VFWR increased the daily mean distance covered by Tg mice eliminating the difference between Tg and WT present before exercise at 12 months of age (WT Pre‐EX 3.62 ± 1.66 vs. Tg Pre‐EX 1.51 ± 1.09 km, P < 0.005; WT Post‐EX 5.72 ± 3.42 vs. Tg Post‐EX 4.17 ± 1.8 km, P > 0.005). This effect was concomitant with an improvement of in vivo cardiac performance [(Cardiac Index (mL/min/cm2): 6 months, untrained‐Tg 0.167 ± 0.005 vs. trained‐Tg 0.21 ± 0.003, P < 0.005; 12 months, untrained‐Tg 0.1 ± 0.009 vs. trained‐Tg 0.133 ± 0.005, P < 0.005]. Such effects were associated with a skeletal muscle antioxidant response effective in preventing oxidative damage induced by CHF at the transition phase (untrained‐Tg 0.438 ± 0.25 vs. trained‐Tg 0.114 ± 0.010, P < 0.05) and with an increased expression of protein control markers (MuRF‐1, untrained‐Tg 1.12 ± 0.29 vs. trained‐Tg 14.14 ± 3.04, P < 0.0001; Atrogin‐1, untrained‐Tg 0.9 ± 0.38 vs. trained‐Tg 7.79 ± 2.03, P < 0.01; Cathepsin L, untrained‐Tg 0.91 ± 0.27 vs. trained‐Tg 2.14 ± 0.55, P < 0.01). At the end‐stage of CHF (14 months), trained‐Tg mice showed a worsening of physical performance (decrease in daily activity and weekly distance and time of activity) compared to trained age‐matched WT in association with oxidative protein damage of a similar level to that of untrained‐Tg mice (untrained‐Tg 0.62 ± 0.24 vs. trained‐Tg 0.64 ± 0.13, P > 0.05). Prolonged voluntary physical activity performed before the onset of CHF end‐stage, appears to be a useful tool to increase cardiac function and to reduce skeletal muscle oxidative damage counteracting physical activity decline.
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Affiliation(s)
- Eleonora Bardi
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Joanna Majerczak
- Department of Muscle Physiology, Faculty of Rehabilitation, University School of Physical Education, Krakow, Poland.,Department of Neurobiology, Poznan University of Physical Education, Poznan, Poland
| | - Jerzy A Zoladz
- Department of Muscle Physiology, Faculty of Rehabilitation, University School of Physical Education, Krakow, Poland
| | - Urszula Tyrankiewicz
- Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University Medical College, Krakow, Poland
| | - Tomasz Skorka
- Department of Magnetic Resonance Imaging, Institute of Nuclear Physics Polish Academy of Sciences, Krakow, Poland
| | - Stefan Chlopicki
- Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University Medical College, Krakow, Poland.,Chair of Pharmacology, Jagiellonian University Medical College, Krakow, Poland
| | - Magdalena Jablonska
- Department of Magnetic Resonance Imaging, Institute of Nuclear Physics Polish Academy of Sciences, Krakow, Poland
| | - Anna Bar
- Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University Medical College, Krakow, Poland
| | - Krzysztof Jasinski
- Department of Magnetic Resonance Imaging, Institute of Nuclear Physics Polish Academy of Sciences, Krakow, Poland
| | - Alessia Buso
- Department of Medicine, University of Udine, Udine, Italy
| | - Desy Salvadego
- Department of Medicine, University of Udine, Udine, Italy
| | - Zenon Nieckarz
- Department of Muscle Physiology, Faculty of Rehabilitation, University School of Physical Education, Krakow, Poland
| | - Bruno Grassi
- Department of Medicine, University of Udine, Udine, Italy.,Institute of Bioimaging and Molecular Physiology, National Research Council, Milano, Italy
| | - Roberto Bottinelli
- Department of Molecular Medicine, University of Pavia, Pavia, Italy.,Fondazione Salvatore Maugeri (IRCCS), Scientific Institute of Pavia, Pavia, Italy.,Interdipartimental Centre for Biology and Sport Medicine, University of Pavia, Pavia, Italy
| | - Maria Antonietta Pellegrino
- Department of Molecular Medicine, University of Pavia, Pavia, Italy.,Interdipartimental Centre for Biology and Sport Medicine, University of Pavia, Pavia, Italy.,Interuniversity Institute of Myology, University of Pavia, Pavia, Italy
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Gomes MJ, Pagan LU, Lima ARR, Reyes DRA, Martinez PF, Damatto FC, Pontes THD, Rodrigues EA, Souza LM, Tosta IF, Fernandes AAH, Zornoff LAM, Okoshi K, Okoshi MP. Effects of aerobic and resistance exercise on cardiac remodelling and skeletal muscle oxidative stress of infarcted rats. J Cell Mol Med 2020; 24:5352-5362. [PMID: 32239667 PMCID: PMC7205792 DOI: 10.1111/jcmm.15191] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 01/21/2020] [Accepted: 02/22/2020] [Indexed: 12/22/2022] Open
Abstract
We compared the influence of aerobic and resistance exercise on cardiac remodelling, physical capacity and skeletal muscle oxidative stress in rats with MI‐induced heart failure. Three months after MI induction, Wistar rats were divided into four groups: Sham; sedentary MI (S‐MI); aerobic exercised MI (A‐MI); and resistance exercised MI (R‐MI). Exercised rats trained three times a week for 12 weeks on a treadmill or ladder. Statistical analysis was performed by ANOVA or Kruskal‐Wallis test. Functional aerobic capacity was greater in A‐MI and strength gain higher in R‐MI. Echocardiographic parameters did not differ between infarct groups. Reactive oxygen species production, evaluated by fluorescence, was higher in S‐MI than Sham, and lipid hydroperoxide concentration was lower in A‐MI than the other groups. Glutathione peroxidase activity was higher in A‐MI than S‐MI and R‐MI. Superoxide dismutase was lower in S‐MI than Sham and R‐MI. Gastrocnemius cross‐sectional area, satellite cell activation and expression of the ubiquitin‐proteasome system proteins did not differ between groups. In conclusion, aerobic exercise and resistance exercise improve functional capacity and maximum load carrying, respectively, without changing cardiac remodelling in infarcted rats. In the gastrocnemius, infarction increases oxidative stress and changes antioxidant enzyme activities. Aerobic exercise reduces oxidative stress and attenuates superoxide dismutase and glutathione peroxidase changes.
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Affiliation(s)
- Mariana J Gomes
- Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Brazil
| | - Luana U Pagan
- Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Brazil
| | - Aline R R Lima
- Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Brazil
| | - David R A Reyes
- Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Brazil
| | - Paula F Martinez
- School of Physical Therapy, Federal University of Mato Grosso do Sul, Campo Grande, Brazil
| | - Felipe C Damatto
- Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Brazil
| | - Thierres H D Pontes
- Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Brazil
| | - Eder A Rodrigues
- Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Brazil
| | - Lidiane M Souza
- Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Brazil
| | - Ingrid F Tosta
- Institute of Biosciences, Sao Paulo State University, UNESP, Botucatu, Brazil
| | - Ana A H Fernandes
- Institute of Biosciences, Sao Paulo State University, UNESP, Botucatu, Brazil
| | | | - Katashi Okoshi
- Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Brazil
| | - Marina P Okoshi
- Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Brazil
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Garnham JO, Roberts LD, Espino-Gonzalez E, Whitehead A, Swoboda PP, Koshy A, Gierula J, Paton MF, Cubbon RM, Kearney MT, Egginton S, Bowen TS, Witte KK. Chronic heart failure with diabetes mellitus is characterized by a severe skeletal muscle pathology. J Cachexia Sarcopenia Muscle 2020; 11:394-404. [PMID: 31863644 PMCID: PMC7113493 DOI: 10.1002/jcsm.12515] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 10/07/2019] [Accepted: 10/17/2019] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Patients with coexistent chronic heart failure (CHF) and diabetes mellitus (DM) demonstrate greater exercise limitation and worse prognosis compared with CHF patients without DM, even when corrected for cardiac dysfunction. Understanding the origins of symptoms in this subgroup may facilitate development of targeted treatments. We therefore characterized the skeletal muscle phenotype and its relationship to exercise limitation in patients with diabetic heart failure (D-HF). METHODS In one of the largest muscle sampling studies in a CHF population, pectoralis major biopsies were taken from age-matched controls (n = 25), DM (n = 10), CHF (n = 52), and D-HF (n = 28) patients. In situ mitochondrial function and reactive oxygen species, fibre morphology, capillarity, and gene expression analyses were performed and correlated to whole-body exercise capacity. RESULTS Mitochondrial respiration, content, coupling efficiency, and intrinsic function were lower in D-HF patients compared with other groups (P < 0.05). A unique mitochondrial complex I dysfunction was present in D-HF patients only (P < 0.05), which strongly correlated to exercise capacity (R2 = 0.64; P < 0.001). Mitochondrial impairments in D-HF corresponded to higher levels of mitochondrial reactive oxygen species (P < 0.05) and lower gene expression of anti-oxidative enzyme superoxide dismutase 2 (P < 0.05) and complex I subunit NDUFS1 (P < 0.05). D-HF was also associated with severe fibre atrophy (P < 0.05) and reduced local fibre capillarity (P < 0.05). CONCLUSIONS Patients with D-HF develop a specific skeletal muscle pathology, characterized by mitochondrial impairments, fibre atrophy, and derangements in the capillary network that are linked to exercise intolerance. These novel preliminary data support skeletal muscle as a potential therapeutic target for treating patients with D-HF.
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Affiliation(s)
- Jack O Garnham
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Lee D Roberts
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Ever Espino-Gonzalez
- School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK
| | - Anna Whitehead
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Peter P Swoboda
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Aaron Koshy
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - John Gierula
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Maria F Paton
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Richard M Cubbon
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Mark T Kearney
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Stuart Egginton
- School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK
| | - T Scott Bowen
- School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK
| | - Klaus K Witte
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
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Affiliation(s)
- Hideo Izawa
- Department of Cardiology, Fujita Health University Bantane Hospital
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Abstract
During aging, deterioration in cardiac structure and function leads to increased susceptibility to heart failure. The need for interventions to combat this age-related cardiac decline is becoming increasingly urgent as the elderly population continues to grow. Our understanding of cardiac aging, and aging in general, is limited. However, recent studies of age-related decline and its prevention through interventions like exercise have revealed novel pathological and cardioprotective pathways. In this review, we summarize recent findings concerning the molecular mechanisms of age-related heart failure and highlight exercise as a valuable experimental platform for the discovery of much-needed novel therapeutic targets in this chronic disease.
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Affiliation(s)
- Haobo Li
- From the Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., M.H.H., J.R., L.E.T., J.D.R., A.R.)
| | - Margaret H Hastings
- From the Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., M.H.H., J.R., L.E.T., J.D.R., A.R.)
| | - James Rhee
- From the Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., M.H.H., J.R., L.E.T., J.D.R., A.R.).,Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston (J.R.)
| | - Lena E Trager
- From the Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., M.H.H., J.R., L.E.T., J.D.R., A.R.)
| | - Jason D Roh
- From the Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., M.H.H., J.R., L.E.T., J.D.R., A.R.)
| | - Anthony Rosenzweig
- From the Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston (H.L., M.H.H., J.R., L.E.T., J.D.R., A.R.)
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