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Varghese LN, Sheard PW, Schwenke DO, Katare R. Sex-specific dysregulation of cardiac-enriched microRNAs with age in Drosophila melanogaster. Am J Physiol Cell Physiol 2025; 328:C1743-C1751. [PMID: 40250483 DOI: 10.1152/ajpcell.00134.2025] [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: 02/12/2025] [Revised: 02/28/2025] [Accepted: 04/10/2025] [Indexed: 04/20/2025]
Abstract
Dysregulation of cardiac-enriched microRNA (miRNA) expression is linked to age-associated cardiovascular diseases (CVDs). However, the sex-specificity and age at which dysregulation occurs remain unclear. Given the conserved nature of miRNAs and short lifespan of Drosophila melanogaster (fruit flies), we investigated age-related changes in the expression of cardiac enriched miRNAs (miR-1, -9, -34a, and -133, target miRNAs) and their impact on the cardiac tube in male and female flies. Cardiac tube tissues were collected from male and female flies (n = 5/group) at 7-day intervals from day 7 to day 70. miRNAs and predicted target mRNA gene (KCNQ, MRTF, and CCN) expression were quantified by RT-qPCR (n = 4-6/group). Myofibril diameter was assessed by Masson's trichrome staining (n = 4-6) to determine the structural effects of hypertrophic miR-9. In females, miR-1 was downregulated with age (P ≤ 0.0001), whereas in males, miR-9 (P ≤ 0.0001) and miR-34a (P = 0.0017) were downregulated. Interestingly, miR-133 was downregulated in both sexes (P ≤ 0.0001). In males, MRTF (miR-9 target) and CCN (miR-133 target) expression increased with age (P = 0.016 and P = 0.013, respectively), whereas in females, KCNQ (miR-1 target) and CCN expression decreased (P = 0.03 and P = 0.002, respectively). Myofibril thickness significantly increased with age in both sexes (P < 0.0001). miR-9 downregulation may contribute to this effect in males, whereas the mechanism in females remains unclear. This study provides novel insights into sex-specific miRNA dysregulation in cardiac aging, emphasizing the need to consider sex differences in miRNA-mediated cardiovascular aging and the potential of miRNAs as diagnostic tools in age-related CVDs.NEW & NOTEWORTHY Advancements in healthcare and diet have increased life expectancy, doubling the population aged 60 and above by 2050. However, this longevity raises the risk of chronic diseases, especially cardiovascular diseases. We examined age-related changes in cardiovascular-enriched microRNAs in the Drosophila melanogaster heart. This first-of-its-kind observational study tracks microRNA changes across life stages. It highlights sex-specific expression of miRNAs, providing crucial insights into cardiac aging. It lays a strong foundation for future research on microRNA in heart health.
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Affiliation(s)
- Lijo N Varghese
- Department of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
| | - Philip W Sheard
- Department of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
| | - Daryl O Schwenke
- Department of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
| | - Rajesh Katare
- Department of Physiology, HeartOtago, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
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2
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Popat A, Jnaneswaran G, Sathipati SY, Sharma PP. MicroRNAs in cardiac arrhythmias: mechanisms, biomarkers and, therapeutic frontiers. Heart Rhythm 2025:S1547-5271(25)02512-3. [PMID: 40449816 DOI: 10.1016/j.hrthm.2025.05.052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2025] [Revised: 05/09/2025] [Accepted: 05/24/2025] [Indexed: 06/03/2025]
Abstract
MicroRNAs (miRNAs) are essential modulators of cardiac arrhythmias, influencing electrical remodeling, ion channel dynamics, and fibrosis. Dysregulated miRNAs, including miR-1, miR-21, and miR-328, contribute to arrhythmogenesis through altered ion channel expression, heightened fibrosis, and inflammation. Recent investigations have identified novel circulating miRNA signatures-such as hsa-miR-96-5p and hsa-miR-184 for post-operative atrial fibrillation (POAF) post-coronary artery bypass grafting, offering high predictive accuracy and targeting pathways like MAPK and TGF-β, as revealed by biological pathway analysis. These miRNAs serve as noninvasive biomarkers for early risk assessment. Therapeutically, miRNA inhibitors and mimics, enhanced by nanoparticle and viral vector delivery, provide targeted interventions. Despite challenges in specificity and delivery, miRNA-based approaches hold transformative potential for arrhythmia diagnosis and personalized management.
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Affiliation(s)
- Apurva Popat
- Department of Internal Medicine, Marshfield Clinic Health System, Marshfield, WI, 54449, USA
| | - Geethu Jnaneswaran
- Department of Internal Medicine, Marshfield Clinic Health System, Marshfield, WI, 54449, USA
| | | | - Param P Sharma
- Department of Cardiology, Marshfield Clinic Health System, Marshfield, WI, 54449, USA.
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Bálint T, Ruppert M, Ágg B, Nagy D, Pálóczi K, Szenthe K, Bánáti F, Sayour AA, Oláh A, Barta BA, Barallobre-Barreiro J, Ferdinandy P, Merkely B, Radovits T. Atrial fibrillation is not associated with altered left atrial microRNA expression profile in advanced heart failure patients. Heart Rhythm 2025:S1547-5271(25)02501-9. [PMID: 40412601 DOI: 10.1016/j.hrthm.2025.05.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 05/02/2025] [Accepted: 05/15/2025] [Indexed: 05/27/2025]
Abstract
BACKGROUND Atrial fibrillation (AF) is common in patients with chronic heart failure (HF). Nevertheless, some patients with HF remain in sinus rhythm (SR) even with marked left atrial (LA) dilatation and fibrosis. The underlying mechanisms for the differences in atrial arrhythmogenicity are poorly uncovered. Recent findings indicate that distinct microRNAs (miRNA) might induce LA structural and molecular alterations. However, the impact of miRNA dysregulation on AF development in the context of HF has not been studied independently of LA remodeling. OBJECTIVE This study aimed to evaluate the differences in LA miRNA expressions in HF patients with AF or SR. METHODS LA myocardial samples were obtained from advanced HF patients with AF (n=12; paroxysmal n=4, chronic as persistent/permanent n=8) or SR (n=12) undergoing heart transplantation. The extent of LA interstitial fibrosis was evaluated using picrosirius red-staining. The LA load was estimated by measuring LA mRNA expression of the NPPA gene encoding atrial natriuretic peptide with qRT-PCR and circulating N-terminal proatrial natriuretic peptide (NT-proANP) by ELISA. The LA miRNA screening was performed using the NanoString technology. RESULTS LA dilatation, fibrosis, NPPA gene expression, as well as circulating NT-proANP levels were similar between the AF and SR groups, suggesting a comparable extent of atrial remodeling and load among the study groups. The miRNA analysis revealed no differences in atrial miRNA expression between the groups, even after AF subgroup analysis. CONCLUSION The LA miRNA expression profile shows no distinction between AF and SR in advanced HF patients with similar levels of pathological atrial remodeling.
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Affiliation(s)
- Tímea Bálint
- Department of Cardiology, Heart and Vascular Center, Semmelweis University, Budapest, Hungary; Department of Surgical Research and Techniques, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Mihály Ruppert
- Department of Cardiology, Heart and Vascular Center, Semmelweis University, Budapest, Hungary; Department of Surgical Research and Techniques, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
| | - Bence Ágg
- Cardiometabolic and HUN-REN-SU System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary; Center for Pharmacology and Drug Research & Development, Semmelweis University, Budapest, Hungary; Pharmahungary Group, Szeged, Hungary
| | - Dávid Nagy
- Department of Cardiology, Heart and Vascular Center, Semmelweis University, Budapest, Hungary; Department of Surgical Research and Techniques, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Krisztina Pálóczi
- Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary
| | - Kálmán Szenthe
- Microbiology Laboratory, County Hospital Győr, Petz Aladár Hospital, Győr, Hungary
| | | | - Alex Ali Sayour
- Department of Cardiology, Heart and Vascular Center, Semmelweis University, Budapest, Hungary; Department of Surgical Research and Techniques, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Attila Oláh
- Department of Cardiology, Heart and Vascular Center, Semmelweis University, Budapest, Hungary; Department of Surgical Research and Techniques, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Bálint András Barta
- Department of Cardiology, Heart and Vascular Center, Semmelweis University, Budapest, Hungary; Department of Surgical Research and Techniques, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Javier Barallobre-Barreiro
- King's British Heart Foundation Centre of Research Excellence, King's College London, London, United Kingdom
| | - Péter Ferdinandy
- Cardiometabolic and HUN-REN-SU System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary; Center for Pharmacology and Drug Research & Development, Semmelweis University, Budapest, Hungary; Pharmahungary Group, Szeged, Hungary
| | - Béla Merkely
- Department of Cardiology, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Tamás Radovits
- Department of Cardiology, Heart and Vascular Center, Semmelweis University, Budapest, Hungary; Department of Surgical Research and Techniques, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
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Shang W, Geng X, Sun X, Fan X, Li A, Zhang C, Kang Y, Liang Y, Zhang J. Non-coding RNAs modulate pyroptosis in diabetic cardiomyopathy: A comprehensive review. Int J Biol Macromol 2025; 309:142865. [PMID: 40188918 DOI: 10.1016/j.ijbiomac.2025.142865] [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: 01/01/2025] [Revised: 02/07/2025] [Accepted: 04/03/2025] [Indexed: 04/11/2025]
Abstract
Diabetic cardiomyopathy (DCM) is a leading cause of heart failure (HF) among individuals with diabetes, presenting a significant medical challenge due to its complex pathophysiology and the lack of targeted therapies. Pyroptosis, a pro-inflammatory form of programmed cell death (PCD), is the predominant mode of cell death in the primary resident cells involved in DCM. It has been reported to be critical in DCM's onset, progression, and pathogenesis. Non-coding RNAs (ncRNAs), diverse transcripts lacking protein-coding potential, are essential for cellular physiology and the progression of various diseases. Increasing evidence indicates that ncRNAs are pivotal in the pathogenesis of DCM by regulating pyroptosis. This observation suggests that targeting the regulation of pyroptosis by ncRNAs may offer a novel therapeutic approach for DCM. However, a comprehensive review of this topic is currently lacking. Our objective is to elucidate the regulatory role of ncRNAs in pyroptosis associated with DCM and to elucidate the relationships among these factors. Additionally, we explored how ncRNAs influence pyroptosis and contribute to the pathophysiology of DCM. By doing so, we aim to identify new research targets for the clinical diagnosis and treatment of DCM.
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Affiliation(s)
- Wenyu Shang
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China
| | - Xiaofei Geng
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China
| | - Xitong Sun
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China
| | - Xinbiao Fan
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China
| | - Aolin Li
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China
| | - Chi Zhang
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China
| | - Yuxin Kang
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China
| | - Yongchun Liang
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China
| | - Junping Zhang
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300000, China.
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Ghosh P, Dey A, Nandi S, Majumder R, Das S, Mandal M. CTGF (CCN2): a multifaceted mediator in breast cancer progression and therapeutic targeting. Cancer Metastasis Rev 2025; 44:32. [PMID: 39945880 DOI: 10.1007/s10555-025-10248-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Accepted: 02/01/2025] [Indexed: 03/28/2025]
Abstract
Breast cancer, with its diverse subtypes like ER-positive, HER-2-positive, and triple-negative, presents complex challenges demanding personalized treatment approaches. The intricate interplay of genetic, environmental, and lifestyle factors underscores its status as a primary contributor to cancer-related fatalities in women globally. Understanding the molecular drivers specific to each subtype is crucial for developing effective therapies. In this landscape, connective tissue growth factor (CTGF), also referred to as cellular communication network factor 2 (CCN2), emerges as a significant player. CTGF regulates critical biological activities like cell growth, invasion, and migration, impacting breast cancer development and progression. It modulates breast tumor microenvironment by promoting angiogenesis, activating cancer-associated fibroblasts (CAFs), and inducing inflammation. The activity of CTGF depends on several factors including oxygen levels, hormone signals, and growth factors and differs according to the type of breast cancer. CTGF can regulate breast cancer cells by activating various signaling pathways and modulating the transcription of other genes that are involved in tumor development and metastasis including S100A4, glucose transporter 3 (GLUT3), and vascular endothelial growth factor (VEGF). The matricellular protein can be considered a potential therapeutic target, as it can promote tumor growth and confer drug resistance in breast cancer. Numerous tactics, including neutralizing antibodies, antisense oligonucleotides, natural compounds, recombinant proteins, and short hairpin RNAs have been suggested to block its function. This review highlights the structure of CTGF, regulation of its expression, and current knowledge of its oncogenic role in breast cancer, as well as focusing on potential therapeutic strategies for targeting CTGF in breast cancer.
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Affiliation(s)
- Priya Ghosh
- Cancer Biology Lab, School of Medical Science & Technology, Indian Institute of Technology, Kharagpur 721302, Kharagpur, West Bengal, India
| | - Ankita Dey
- Cancer Biology Lab, School of Medical Science & Technology, Indian Institute of Technology, Kharagpur 721302, Kharagpur, West Bengal, India
| | - Suvendu Nandi
- Cancer Biology Lab, School of Medical Science & Technology, Indian Institute of Technology, Kharagpur 721302, Kharagpur, West Bengal, India
| | - Ranabir Majumder
- Cancer Biology Lab, School of Medical Science & Technology, Indian Institute of Technology, Kharagpur 721302, Kharagpur, West Bengal, India
| | - Subhayan Das
- Department of Allied Health Sciences, Brainware University, Kolkata 700125, Barasat, West Bengal, India
| | - Mahitosh Mandal
- Cancer Biology Lab, School of Medical Science & Technology, Indian Institute of Technology, Kharagpur 721302, Kharagpur, West Bengal, India.
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Yue ZJ, Li XR, Shi Z, Li XW. Myocardial ferroptosis may exacerbate the progression of atrial fibrillation through isolevuglandins. Eur J Med Res 2025; 30:93. [PMID: 39940048 PMCID: PMC11823066 DOI: 10.1186/s40001-025-02302-2] [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: 02/27/2024] [Accepted: 01/16/2025] [Indexed: 02/14/2025] Open
Abstract
Atrial fibrillation (AF) poses a serious health threat to human health and causes various adverse effects. It is currently the most common type of arrhythmia in adults. Long-term AF induces a series of heart-remodeling events, including mainly cardiac structural remodeling and electrical remodeling, which further exacerbates AF. The oxidative stress has been shown to play a role in inducing myocardial remodeling and the progression of AF. Recent studies have shown that ferroptosis occurs in the myocardium of patients with AF, which exacerbates oxidative stress and may constitute a new mechanism for the progression of AF. However, it is unknown to us how ferroptosis is involved in the initiation and maintenance of AF, so the purpose of this review is to elucidate the possible underlying mechanism of ferroptosis exacerbating AF. We reviewed the latest studies on myocardial ferroptosis and AF and speculate that the lipid peroxidation products isolevuglandins (IsoLGs), which are produced during myocardial ferroptosis, may be involved in the progression of AF through two pathways: (1) IsoLGs inhibit the degradation of myocardial collagen, worsening myocardial fibrosis; and (2) IsoLGs promote the occurrence of amyloidosis in the myocardium and increase the risk of AF. Consequently, we aim to prevent the progression of atrial fibrillation by either suppressing the production of IsoLGs or enhancing their clearance process to inhibit ferroptosis in the myocardium, improving the prognosis of patients with AF.
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Affiliation(s)
- Zhi-Jie Yue
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Long Cheng Street 99, Taiyuan, 030032, China
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xin-Ru Li
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Long Cheng Street 99, Taiyuan, 030032, China
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Zhan Shi
- Department of Cardiology, Affiliated Hospital of Army Medical University NCO School, Zhong Shan Road 450, Shijiazhuang, 050047, Hebei, China.
| | - Xue-Wen Li
- Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Long Cheng Street 99, Taiyuan, 030032, China.
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
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Balan AI, Scridon A. MicroRNAs in atrial fibrillation - have we discovered the Holy Grail or opened a Pandora's box? Front Pharmacol 2025; 16:1535621. [PMID: 40012622 PMCID: PMC11861496 DOI: 10.3389/fphar.2025.1535621] [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: 11/27/2024] [Accepted: 01/24/2025] [Indexed: 02/28/2025] Open
Abstract
Atrial fibrillation (AF) causes a heavy socio-economic burden on healthcare systems around the globe. Identification of new preventive, diagnostic, and treatment methods is imperative. In recent years, special attention has been paid to microRNAs (miRNAs) as potential regulators of AF pathogenesis. Through post-transcriptional regulation of genes, miRNAs have been shown to play crucial roles in AF-related structural and electrical atrial remodeling. Altered expression of different miRNAs has been related to proarrhythmic changes in the duration of action potentials and atrial fibrosis. In clinical studies, miRNA changes have been associated with AF, whereas in experimental studies miRNA manipulation has emerged as a potential therapeutic approach. It would appear that, with the advent of miRNAs, we may have found the Holy Grail, and that efficient and personalized AF therapy may be one step away. Yet, the clinical relevance of miRNA evaluation and manipulation remains questionable. Studies have identified numerous miRNAs associated with AF, but none of them have shown sufficient specificity for AF. MicroRNAs are not gene-specific but regulate the expression of a myriad of genes. Cardiac and non-cardiac off-target effects may thus occur following miRNA manipulation. A Pandora's box might thus have opened with the advent of these sophisticated molecules. In this paper, we provide a critical analysis of the clinical and experimental, epidemiological and mechanistic data linking miRNAs to AF, we discuss the most promising miRNA therapeutic approaches, we emphasize a number of questions that remain to be answered, and we identify hotspots for future research.
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Affiliation(s)
| | - Alina Scridon
- Physiology Department and Center for Advanced Medical and Pharmaceutical Research, Pharmacy, Science and Technology “George Emil Palade” of Târgu Mureș, University of Medicine, Târgu Mures, Romania
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Belfiori M, Lazzari L, Hezzell M, Angelini GD, Dong T. Transcriptomics, Proteomics and Bioinformatics in Atrial Fibrillation: A Descriptive Review. Bioengineering (Basel) 2025; 12:149. [PMID: 40001669 PMCID: PMC11851880 DOI: 10.3390/bioengineering12020149] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2025] [Revised: 01/28/2025] [Accepted: 02/02/2025] [Indexed: 02/27/2025] Open
Abstract
Atrial fibrillation (AF) is the most frequent cardiac arrhythmia, with an estimated five million cases globally. This condition increases the likelihood of developing cardiovascular complications such as thromboembolic events, with a fivefold increase in risk of both heart failure and stroke. Contemporary challenges include a better understanding AF pathophysiology and optimizing therapeutical options due to the current lack of efficacy and adverse effects of antiarrhythmic drug therapy. Hence, the identification of novel biomarkers in biological samples would greatly impact the diagnostic and therapeutic opportunities offered to AF patients. Long noncoding RNAs, micro RNAs, circular RNAs, and genes involved in heart cell differentiation are particularly relevant to understanding gene regulatory effects on AF pathophysiology. Proteomic remodeling may also play an important role in the structural, electrical, ion channel, and interactome dysfunctions associated with AF pathogenesis. Different devices for processing RNA and proteomic samples vary from RNA sequencing and microarray to a wide range of mass spectrometry techniques such as Orbitrap, Quadrupole, LC-MS, and hybrid systems. Since AF atrial tissue samples require a more invasive approach to be retrieved and analyzed, blood plasma biomarkers were also considered. A range of different sample preprocessing techniques and bioinformatic methods across studies were examined. The objective of this descriptive review is to examine the most recent developments of transcriptomics, proteomics, and bioinformatics in atrial fibrillation.
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Affiliation(s)
- Martina Belfiori
- School of Medicine and Surgery, Università degli Studi di Milano-Bicocca, 20126 Milano, Italy; (M.B.); (L.L.)
| | - Lisa Lazzari
- School of Medicine and Surgery, Università degli Studi di Milano-Bicocca, 20126 Milano, Italy; (M.B.); (L.L.)
| | - Melanie Hezzell
- Bristol Veterinary School, University of Bristol, Langford House, Langford, Bristol BS40 5DU, UK;
| | - Gianni D. Angelini
- Bristol Heart Institute, Translational Health Sciences, University of Bristol, Bristol BS2 8HW, UK;
| | - Tim Dong
- Bristol Heart Institute, Translational Health Sciences, University of Bristol, Bristol BS2 8HW, UK;
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Bianchi G, Vizio B, Bosco O, Schiavello M, Cagna Vallino P, Rumbolo F, Morello F, Mengozzi G, Montrucchio G, Lupia E, Pivetta E. miR-30d Levels Predict Re-Hospitalization in Patients with Acute Cardiogenic Pulmonary Edema: A Preliminary Study. Int J Mol Sci 2025; 26:1278. [PMID: 39941043 PMCID: PMC11818144 DOI: 10.3390/ijms26031278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2025] [Revised: 01/27/2025] [Accepted: 01/29/2025] [Indexed: 02/16/2025] Open
Abstract
Acute cardiogenic pulmonary edema (ACPE) is a common and serious manifestation of heart failure (HF), representing 10-20% of all acute HF admissions. It is associated with elevated in-hospital mortality and high rates of re-hospitalization. MicroRs, like miR-30d, are of particular interest in heart failure due to their regulatory role in gene expression and potential as biomarkers for diagnosing and predicting patient outcomes, especially in high-risk cases such as ACPE. We conducted a cohort study on patients diagnosed with ACPE in the Emergency Department (ED). The circulating levels of miR-30d were analyzed at the time of hospital admission and at one-month follow-up along with other biomarkers. We enrolled 24 ACPE patients and 10 control subjects. Median age was 80.8 years (interquartile range, IQR, 8.2) in ACPE cases, and 78.5 years (IQR 9.8) in controls with a male/female ratio of 2 and 0.66, respectively. In ACPE patients, median cardiac ejection fraction was 42.5%, creatinine 1.63 mg/dL (IQR 1.24), troponin 63.5 ng/dL (58), and NT-proBNP 4243.5 pg/mL (IQR 5846) at ED evaluation. Median concentration of miR30d was 0.81 in controls, and 3.67 and 7.28 in ACPE patients at enrollment time and one month later, respectively. Re-hospitalization occurred in 7 ACPE patients in the following 3 months, and in 9 during the following year. miR-30d had a significant predictive value in assessing the risk of re-hospitalization at both 3 months and 1 year following the initial diagnosis of ACPE, while it did not in assessing the risk of death at 1 year. When compared with the other biomarkers, none of them showed a better accuracy than miR-30d. Our findings suggest that elevated levels of miR-30d are associated with an increased rate of hospital readmission at both 3 months and 1 year after discharge. Larger, multicenter studies will be needed to confirm the validity of circulating miR-30d levels as a potential biomarker useful for risk prediction in ACPE patients and its utility in improving individualized patient care.
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Affiliation(s)
- Giordano Bianchi
- Division of Emergency Medicine and High Dependency Unit, Città della Salute e della Scienza di Torino, Molinette Hospital, 10126 Turin, Italy; (G.B.); (P.C.V.); (F.M.); (E.L.)
| | - Barbara Vizio
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (B.V.); (O.B.); (M.S.); (G.M.); (G.M.)
| | - Ornella Bosco
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (B.V.); (O.B.); (M.S.); (G.M.); (G.M.)
| | - Martina Schiavello
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (B.V.); (O.B.); (M.S.); (G.M.); (G.M.)
| | - Paolo Cagna Vallino
- Division of Emergency Medicine and High Dependency Unit, Città della Salute e della Scienza di Torino, Molinette Hospital, 10126 Turin, Italy; (G.B.); (P.C.V.); (F.M.); (E.L.)
- Residency Programme in Emergency Medicine, University of Turin, 10126 Turin, Italy
| | - Francesca Rumbolo
- Clinical Biochemistry Laboratory, Città della Salute e della Scienza di Torino, Molinette Hospital, 10126 Turin, Italy;
| | - Fulvio Morello
- Division of Emergency Medicine and High Dependency Unit, Città della Salute e della Scienza di Torino, Molinette Hospital, 10126 Turin, Italy; (G.B.); (P.C.V.); (F.M.); (E.L.)
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (B.V.); (O.B.); (M.S.); (G.M.); (G.M.)
| | - Giulio Mengozzi
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (B.V.); (O.B.); (M.S.); (G.M.); (G.M.)
- Clinical Biochemistry Laboratory, Città della Salute e della Scienza di Torino, Molinette Hospital, 10126 Turin, Italy;
| | - Giuseppe Montrucchio
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (B.V.); (O.B.); (M.S.); (G.M.); (G.M.)
| | - Enrico Lupia
- Division of Emergency Medicine and High Dependency Unit, Città della Salute e della Scienza di Torino, Molinette Hospital, 10126 Turin, Italy; (G.B.); (P.C.V.); (F.M.); (E.L.)
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (B.V.); (O.B.); (M.S.); (G.M.); (G.M.)
| | - Emanuele Pivetta
- Division of Emergency Medicine and High Dependency Unit, Città della Salute e della Scienza di Torino, Molinette Hospital, 10126 Turin, Italy; (G.B.); (P.C.V.); (F.M.); (E.L.)
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy; (B.V.); (O.B.); (M.S.); (G.M.); (G.M.)
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10
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Li D, Hou T, Du X, Zhao L, Zhang L, Gao F, Xing T. Integrated analysis of miRNA and mRNA expression profiles associated with wooden breast myopathy in broiler chickens. Int J Biol Macromol 2025; 284:137990. [PMID: 39603286 DOI: 10.1016/j.ijbiomac.2024.137990] [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: 09/20/2024] [Revised: 11/18/2024] [Accepted: 11/21/2024] [Indexed: 11/29/2024]
Abstract
Wooden breast (WB) myopathy has raised a worldwide concern among broiler industry during the past decade. Despite progress in understanding its etiology from transcriptional regulation, post-transcriptional mechanisms including the regulation of microRNAs (miRNAs) remain largely unknown. In the current study, we described an integrative analysis between mRNA and miRNA expression profiles of pectoralis major muscle from normal and WB myopathic broilers. A total of 1983 differentially expressed mRNAs (DEmRNAs) and 155 DEmiRNAs were identified in WB. We screened crucial biological processes and core DEmRNAs enriched in functional pathways, and established the protein-protein interaction network. DEmiRNAs and negatively correlated DEmRNAs regulatory networks were constructed, including 44 exist DEmiRNAs and 478 DEmRNAs, forming 772 miRNA-mRNA pairs. Upregulated DEmiRNAs including gga-miR-21-3p, gga-miR-460a-5p and gga-miR-6631-5p, as well as downregulated DEmiRNAs including gga-miR-182-5p, gga-miR-183 and gga-miR-96-5p were identified as hub miRNAs. Meanwhile, functional enrichment analysis indicated that upregulated DEmRNAs in the network were enriched in biological processes of response to stimulus, inflammatory response, extracellular matrix organization, whereas downregulated DEmRNAs were enriched in carbohydrate, amino acid and nucleotide metabolic processes. Collectively, our integrative miRNA and mRNA analysis highlighted candidate miRNAs and mRNAs, as well as potential miRNA-mRNA regulatory mechanisms involved in WB myopathy in broiler chicken.
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Affiliation(s)
- Duanduan Li
- College of Animal Science and Technology, Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province, Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Joint International Research Laboratory of Animal Health and Food Safety, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing 210095, China
| | - Taijiang Hou
- College of Animal Science and Technology, Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province, Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Joint International Research Laboratory of Animal Health and Food Safety, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing 210095, China
| | - Xing Du
- College of Animal Science and Technology, Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province, Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Joint International Research Laboratory of Animal Health and Food Safety, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing 210095, China
| | - Liang Zhao
- College of Animal Science and Technology, Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province, Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Joint International Research Laboratory of Animal Health and Food Safety, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing 210095, China
| | - Lin Zhang
- College of Animal Science and Technology, Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province, Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Joint International Research Laboratory of Animal Health and Food Safety, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing 210095, China
| | - Feng Gao
- College of Animal Science and Technology, Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province, Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Joint International Research Laboratory of Animal Health and Food Safety, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing 210095, China
| | - Tong Xing
- College of Animal Science and Technology, Key Laboratory of Animal Origin Food Production and Safety Guarantee of Jiangsu Province, Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control, Joint International Research Laboratory of Animal Health and Food Safety, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing 210095, China.
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11
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Vardas EP, Oikonomou E, Vardas PE, Tousoulis D. MicroRNAs as Prognostic Biomarkers for Atrial Fibrillation Recurrence After Catheter Ablation: Current Evidence and Future Directions. Biomedicines 2024; 13:32. [PMID: 39857616 PMCID: PMC11762821 DOI: 10.3390/biomedicines13010032] [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: 11/26/2024] [Revised: 12/23/2024] [Accepted: 12/25/2024] [Indexed: 01/27/2025] Open
Abstract
Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice and is associated with significant morbidity and mortality. Even though catheter ablation has emerged as an available and effective treatment for AF, recurrence remains a significant challenge. This review presents the existing evidence on the prognostic role of microRNAs (miRNAs) in the prediction of AF recurrence after catheter ablation. We examined studies investigating the association between miRNA expression and post-ablation AF recurrence. Multiple miRNAs have been highlighted as potential biomarkers, which are involved in pathophysiological processes such as atrial remodeling, fibrosis, and inflammation. Despite some promising results, there has been significant heterogeneity across the studies. In this review, we demonstrate the potential miRNAs that can be routinely used as biomarkers of AF recurrence, and we identify areas that require further research to validate their clinical utility.
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Affiliation(s)
- Emmanouil P. Vardas
- 1st Cardiology Department, General Hospital of Athens “Hippokration”, University of Athens Medical School, 11528 Athens, Greece;
- Department of Cardiology, General Hospital of Athens “G. Gennimatas”, 11527 Athens, Greece
| | - Evangelos Oikonomou
- 3rd Cardiology Department, Sotiria Regional Hospital for Chest Diseases, University of Athens Medical School, 11527 Athens, Greece
| | - Panos E. Vardas
- Biomedical Research Foundation Academy of Athens, Heart Sector, Hygeia Hospitals Group, Attica, 15123 Athens, Greece
| | - Dimitris Tousoulis
- 1st Cardiology Department, General Hospital of Athens “Hippokration”, University of Athens Medical School, 11528 Athens, Greece;
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12
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Schoettler FI, Fatehi Hassanabad A, Jadli AS, Patel VB, Fedak PWM. Exploring the role of pericardial miRNAs and exosomes in modulating cardiac fibrosis. Cardiovasc Pathol 2024; 73:107671. [PMID: 38906439 DOI: 10.1016/j.carpath.2024.107671] [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: 03/31/2024] [Revised: 05/26/2024] [Accepted: 06/15/2024] [Indexed: 06/23/2024] Open
Abstract
The potential of the pericardial space as a therapeutic delivery tool for cardiac fibrosis and heart failure (HF) treatment has yet to be elucidated. Recently, miRNAs and exosomes have been discovered to be present in human pericardial fluid (PF). Novel studies have shown characteristic human PF miRNA compositions associated with cardiac diseases and higher miRNA expressions in PF compared to peripheral blood. Five key studies found differentially expressed miRNAs in HF, angina pectoris, aortic stenosis, ventricular tachycardia, and congenital heart diseases with either atrial fibrillation or sinus rhythm. As miRNA-based therapeutics for cardiac fibrosis and HF showed promising results in several in vivo studies for multiple miRNAs, we hypothesize a potential role of miRNA-based therapeutics delivered through the pericardial cavity. This is underlined by the favorable results of the first phase 1b clinical trial in this emerging field. Presenting the first human miRNA antisense drug trial, inhibition of miR-132 by intravenous administration of a novel antisense oligonucleotide, CDR132L, established efficacy in reducing miR-132 in plasma samples in a dose-dependent manner. We screened the literature, provided an overview of the miRNAs and exosomes present in PF, and drew a connection to those miRNAs previously elucidated in cardiac fibrosis and HF. Further, we speculate about clinical implications and potential delivery methods.
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Affiliation(s)
- Friederike I Schoettler
- Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada; Department of Cardiac Surgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany
| | - Ali Fatehi Hassanabad
- Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada; Department of Cardiac Sciences, Section of Cardiac Surgery, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Anshul S Jadli
- Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada; Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Vaibhav B Patel
- Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada; Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Paul W M Fedak
- Department of Cardiac Sciences, Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada; Department of Cardiac Sciences, Section of Cardiac Surgery, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
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13
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Song R, Zhang L. MicroRNAs and therapeutic potentials in acute and chronic cardiac disease. Drug Discov Today 2024; 29:104179. [PMID: 39276921 DOI: 10.1016/j.drudis.2024.104179] [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: 06/18/2024] [Revised: 08/23/2024] [Accepted: 09/10/2024] [Indexed: 09/17/2024]
Abstract
microRNAs (miRNAs) are small regulatory RNAs implicated in various cardiac disorders. In this review, the role of miRNAs is discussed in relation to acute myocardial infarction and chronic heart failure. In both settings, miRNAs are altered, contributing to injury and adverse remodeling. Notably, miRNA profiles differ between acute ischemic injury and progressive heart failure. Owing to miRNA variabilities between disease stages and delivery difficulties, translation of animal studies to the clinic remains challenging. The identification of distinct miRNA signatures could lead to the development of miRNA therapies tailored to different disease stages. Here, we summarize the current understanding of miRNAs in acute and chronic cardiac diseases, identify knowledge gaps and discuss progress in developing miRNA-based treatment strategies.
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Affiliation(s)
- Rui Song
- Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.
| | - Lubo Zhang
- Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.
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14
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El Khayari A, Hakam SM, Malka G, Rochette L, El Fatimy R. New insights into the cardio-renal benefits of SGLT2 inhibitors and the coordinated role of miR-30 family. Genes Dis 2024; 11:101174. [PMID: 39224109 PMCID: PMC11367061 DOI: 10.1016/j.gendis.2023.101174] [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: 02/01/2023] [Revised: 09/15/2023] [Accepted: 10/10/2023] [Indexed: 09/04/2024] Open
Abstract
Sodium-glucose co-transporter inhibitors (SGLTis) are the latest class of anti-hyperglycemic agents. In addition to inhibiting the absorption of glucose by the kidney causing glycosuria, these drugs also demonstrate cardio-renal benefits in diabetic subjects. miR-30 family, one of the most abundant microRNAs in the heart, has recently been linked to a setting of cardiovascular diseases and has been proposed as novel biomarkers in kidney dysfunctions as well; their expression is consistently dysregulated in a variety of cardio-renal dysfunctions. The mechanistic involvement and the potential interplay between miR-30 and SGLT2i effects have yet to be thoroughly elucidated. Recent research has stressed the relevance of this cluster of microRNAs as modulators of several pathological processes in the heart and kidneys, raising the possibility of these small ncRNAs playing a central role in various cardiovascular complications, notably, endothelial dysfunction and pathological remodeling. Here, we review current evidence supporting the pleiotropic effects of SGLT2is in cardiovascular and renal outcomes and investigate the link and the coordinated implication of the miR-30 family in endothelial dysfunction and cardiac remodeling. We also discuss the emerging role of circulating miR-30 as non-invasive biomarkers and attractive therapeutic targets for cardiovascular diseases and kidney diseases. Clinical evidence, as well as metabolic, cellular, and molecular aspects, are comprehensively covered.
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Affiliation(s)
- Abdellatif El Khayari
- Institute of Biological Sciences (ISSB-P), UM6P Faculty of Medical Sciences, Mohammed VI Polytechnic University (UM6P), Ben-Guerir 43150, Morocco
| | - Soukaina Miya Hakam
- Institute of Biological Sciences (ISSB-P), UM6P Faculty of Medical Sciences, Mohammed VI Polytechnic University (UM6P), Ben-Guerir 43150, Morocco
| | - Gabriel Malka
- Institute of Biological Sciences (ISSB-P), UM6P Faculty of Medical Sciences, Mohammed VI Polytechnic University (UM6P), Ben-Guerir 43150, Morocco
| | - Luc Rochette
- Equipe d'Accueil (EA 7460): Physiopathologie et Epidémiologie Cérébro-Cardiovasculaires (PEC2), Université de Bourgogne – Franche Comté, Faculté des Sciences de Santé, 7 Bd Jeanne d'Arc, Dijon 21000, France
| | - Rachid El Fatimy
- Institute of Biological Sciences (ISSB-P), UM6P Faculty of Medical Sciences, Mohammed VI Polytechnic University (UM6P), Ben-Guerir 43150, Morocco
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15
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Fatehi Hassanabad A, Zarzycki AN, Patel VB, Fedak PWM. Current concepts in the epigenetic regulation of cardiac fibrosis. Cardiovasc Pathol 2024; 73:107673. [PMID: 38996851 DOI: 10.1016/j.carpath.2024.107673] [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: 02/16/2024] [Revised: 06/18/2024] [Accepted: 07/07/2024] [Indexed: 07/14/2024] Open
Abstract
Cardiac fibrosis is a significant driver of congestive heart failure, a syndrome that continues to affect a growing patient population globally. Cardiac fibrosis results from a constellation of complex processes at the transcription, receptor, and signaling axes levels. Various mediators and signaling cascades, such as the transformation growth factor-beta pathway, have been implicated in the pathophysiology of cardiac tissue fibrosis. Our understanding of these markers and pathways has improved in recent years as more advanced technologies and assays have been developed, allowing for better delineation of the crosstalk between specific factors. There is mounting evidence suggesting that epigenetic modulation plays a pivotal role in the progression of cardiac fibrosis. Transcriptional regulation of key pro- and antifibrotic pathways can accentuate or blunt the rate and extent of fibrosis at the tissue level. Exosomes, micro-RNAs, and long noncoding RNAs all belong to factors that can impact the epigenetic signature in cardiac fibrosis. Herein, we comprehensively review the latest literature about exosomes, their contents, and cardiac fibrosis. In doing so, we highlight the specific transcriptional factors with pro- or antifibrotic properties. We also assimilate the data supporting these mediators' potential utility as diagnostic or prognostic biomarkers. Finally, we offer insight into where further work can be done to fill existing gaps to translate preclinical findings better and improve clinical outcomes.
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Affiliation(s)
- Ali Fatehi Hassanabad
- Section of Cardiac Surgery, Department of Cardiac Science, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Anna N Zarzycki
- Section of Cardiac Surgery, Department of Cardiac Science, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Vaibhav B Patel
- Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Paul W M Fedak
- Section of Cardiac Surgery, Department of Cardiac Science, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
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16
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Mustafa R, Mens MMJ, van Hilten A, Huang J, Roshchupkin G, Huan T, Broer L, van Meurs JBJ, Elliott P, Levy D, Ikram MA, Evangelou M, Dehghan A, Ghanbari M. A comprehensive study of genetic regulation and disease associations of plasma circulatory microRNAs using population-level data. Genome Biol 2024; 25:276. [PMID: 39434104 PMCID: PMC11492503 DOI: 10.1186/s13059-024-03420-6] [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: 07/13/2023] [Accepted: 10/09/2024] [Indexed: 10/23/2024] Open
Abstract
BACKGROUND MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Perturbations in plasma miRNA levels are known to impact disease risk and have potential as disease biomarkers. Exploring the genetic regulation of miRNAs may yield new insights into their important role in governing gene expression and disease mechanisms. RESULTS We present genome-wide association studies of 2083 plasma circulating miRNAs in 2178 participants of the Rotterdam Study to identify miRNA-expression quantitative trait loci (miR-eQTLs). We identify 3292 associations between 1289 SNPs and 63 miRNAs, of which 65% are replicated in two independent cohorts. We demonstrate that plasma miR-eQTLs co-localise with gene expression, protein, and metabolite-QTLs, which help in identifying miRNA-regulated pathways. We investigate consequences of alteration in circulating miRNA levels on a wide range of clinical conditions in phenome-wide association studies and Mendelian randomisation using the UK Biobank data (N = 423,419), revealing the pleiotropic and causal effects of several miRNAs on various clinical conditions. In the Mendelian randomisation analysis, we find a protective causal effect of miR-1908-5p on the risk of benign colon neoplasm and show that this effect is independent of its host gene (FADS1). CONCLUSIONS This study enriches our understanding of the genetic architecture of plasma miRNAs and explores the signatures of miRNAs across a wide range of clinical conditions. The integration of population-based genomics, other omics layers, and clinical data presents opportunities to unravel potential clinical significance of miRNAs and provides tools for novel miRNA-based therapeutic target discovery.
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Affiliation(s)
- Rima Mustafa
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- UK Dementia Research Institute, Imperial College London, London, UK
- Big Data Institute, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Michelle M J Mens
- Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
- Department of Social and Behavorial Sciences, Harvard T.H Chan School of Public Health, Boston, MA, USA
| | - Arno van Hilten
- Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Jian Huang
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- Institute for Human Development and Potential (IHDP), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore
- Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore
| | - Gennady Roshchupkin
- Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
- Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Tianxiao Huan
- Framingham Heart Study, Framingham, MA, USA
- Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - Linda Broer
- Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Joyce B J van Meurs
- Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
- Department of Orthopaedics and Sports Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Paul Elliott
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- UK Dementia Research Institute, Imperial College London, London, UK
- MRC Centre for Environment and Health, Imperial College London, London, UK
- Health Data Research (HDR) UK, Imperial College London, London, UK
- BHF Centre for Research Excellence, Imperial College London, London, UK
| | - Daniel Levy
- Framingham Heart Study, Framingham, MA, USA
- Population Sciences Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
| | - M Arfan Ikram
- Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | | | - Abbas Dehghan
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
- UK Dementia Research Institute, Imperial College London, London, UK
- MRC Centre for Environment and Health, Imperial College London, London, UK
| | - Mohsen Ghanbari
- Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
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17
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Iacobescu L, Ciobanu AO, Corlatescu AD, Simionescu M, Iacobescu GL, Dragomir E, Vinereanu D. The Role of Circulating MicroRNAs in Cardiovascular Diseases: A Novel Biomarker for Diagnosis and Potential Therapeutic Targets? Cureus 2024; 16:e64100. [PMID: 39114238 PMCID: PMC11305655 DOI: 10.7759/cureus.64100] [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] [Accepted: 07/08/2024] [Indexed: 08/10/2024] Open
Abstract
MicroRNAs, involved in a large variety of pathological conditions, tend to be potential specific biomarkers in cardiovascular diseases. Moreover, these short, non-coding RNAs, regulate post-transcriptional gene expression and protein synthesis, making them ideal for therapeutic targets. Down-regulation and up-regulation of specific microRNAs are currently studied as a novel approach to the diagnosis and treatment of cardiovascular diseases, such as chronic and acute coronary syndromes, atherosclerosis, heart failure, and arrhythmia. MicroRNAs are interesting and attractive targets for cardiovascular-associated therapeutics because of their stability, tissue-specific expression pattern, and secretion of body fluids. Extended research on their isolation, detection, and function will provide the standardization needed for using microRNAs as biomarkers and potential therapeutic targets. This review will summarize recent data on the implication of microRNAs in cardiovascular diseases, their potential role as biomarkers for diagnosis, and also the challenges of using microRNAs as future therapeutic targets.
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Affiliation(s)
- Loredana Iacobescu
- Cardiology, University of Medicine and Pharmacy "Carol Davila", Bucharest, ROU
- Cardiology, University Emergency Hospital, University of Medicine and Pharmacy "Carol Davila", Bucharest, ROU
| | - Andreea-Olivia Ciobanu
- Cardiology, University of Medicine and Pharmacy "Carol Davila", Bucharest, ROU
- Cardiology, University Emergency Hospital, University of Medicine and Pharmacy "Carol Davila", Bucharest, ROU
| | | | - Maya Simionescu
- Biology, Institute of Cellular Biology and Pathology "Nicolae Simionescu", Bucharest, ROU
| | - Georgian L Iacobescu
- Orthopedics and Traumatology, University Emergency Hospital, University of Medicine and Pharmacy "Carol Davila", Bucharest, ROU
| | - Elena Dragomir
- Cellular Biology, Institute of Cellular Biology and Pathology "Nicolae Simionescu", Bucharest, ROU
| | - Dragos Vinereanu
- Cardiology, University of Medicine and Pharmacy "Carol Davila", Bucharest, ROU
- Cardiology, University Emergency Hospital, University of Medicine and Pharmacy "Carol Davila", Bucharest, ROU
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18
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Basak S, Mallick R, Navya Sree B, Duttaroy AK. Placental Epigenome Impacts Fetal Development: Effects of Maternal Nutrients and Gut Microbiota. Nutrients 2024; 16:1860. [PMID: 38931215 PMCID: PMC11206482 DOI: 10.3390/nu16121860] [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: 05/02/2024] [Revised: 06/07/2024] [Accepted: 06/11/2024] [Indexed: 06/28/2024] Open
Abstract
Evidence is emerging on the role of maternal diet, gut microbiota, and other lifestyle factors in establishing lifelong health and disease, which are determined by transgenerationally inherited epigenetic modifications. Understanding epigenetic mechanisms may help identify novel biomarkers for gestation-related exposure, burden, or disease risk. Such biomarkers are essential for developing tools for the early detection of risk factors and exposure levels. It is necessary to establish an exposure threshold due to nutrient deficiencies or other environmental factors that can result in clinically relevant epigenetic alterations that modulate disease risks in the fetus. This narrative review summarizes the latest updates on the roles of maternal nutrients (n-3 fatty acids, polyphenols, vitamins) and gut microbiota on the placental epigenome and its impacts on fetal brain development. This review unravels the potential roles of the functional epigenome for targeted intervention to ensure optimal fetal brain development and its performance in later life.
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Affiliation(s)
- Sanjay Basak
- Molecular Biology Division, ICMR-National Institute of Nutrition, Indian Council of Medical Research, Hyderabad 500007, India; (S.B.); (B.N.S.)
| | - Rahul Mallick
- A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland;
| | - Boga Navya Sree
- Molecular Biology Division, ICMR-National Institute of Nutrition, Indian Council of Medical Research, Hyderabad 500007, India; (S.B.); (B.N.S.)
| | - Asim K. Duttaroy
- Department of Nutrition, Institute of Medical Sciences, Faculty of Medicine, University of Oslo, 0317 Oslo, Norway
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19
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Assayag E, Gurt I, Cohen-Kfir E, Stokar J, Zwas DR, Dresner-Pollak R. Cardiac Left Ventricular miRNA-26a Is Downregulated in Ovariectomized Mice, Upregulated upon 17-Beta Estradiol Replacement, and Inversely Correlated with Collagen Type 1 Gene Expression. Int J Mol Sci 2024; 25:5153. [PMID: 38791190 PMCID: PMC11121197 DOI: 10.3390/ijms25105153] [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: 03/30/2024] [Revised: 04/26/2024] [Accepted: 04/29/2024] [Indexed: 05/26/2024] Open
Abstract
Heart failure with preserved ejection fraction (HFpEF) is more prevalent in post- compared to pre-menopausal women. The underlying mechanisms are not fully understood. Data in humans is confounded by age and co-morbidities. We investigated the effects of ovariectomy and estrogen replacement on the left ventricular (LV) gene expression of pro-inflammatory and pro-fibrotic factors involved in HFpEF and putative regulating miRNAs. Nine-week-old C57BL/6 female mice were subjected to ovariectomy (OVX) or SHAM operation. OVX and SHAM groups were sacrificed 1-, 6-, and 12-weeks post-surgery (T1/SHAM; T1/OVX; T6/SHAM; T6/OVX, T12/SHAM). 17β-estradiol (E2) or vehicle (VEH) was then administered to the OVX groups for 6 weeks (T12/OVX/E2; T12/OVX/VEH). Another SHAM group was sacrificed 12-weeks post-surgery. RNA and miRNAs were extracted from the LV apex. An early 3-fold increase in the gene expression of IL-1α, IL-6, Mmp9, Mmp12, Col1α1, and Col3α1 was observed one-week post-surgery in T1/OVX vs. T1/SHAM, but not at later time points. miRNA-26a was lower in T1/OVX vs. T1/SHAM and was inversely correlated with Col1α1 and Col3α1 expression 1-week post-surgery (r = -0.79 p < 0.001; r = -0.6 p = 0.007). miRNAs-26a, 29b, and 133a were significantly higher, while Col1α1, Col3α1, IL-1α, IL-6, Tnfα, Mmp12, and FasL gene expression was significantly lower in E2- compared to vehicle-treated OVX mice. miRNA-26a was inversely correlated with Col3α1 in T12/OVX/ E2 (r = -0.56 p = 0.02). OVX triggered an early increase in the gene expression of pro-inflammatory and pro-fibrotic factors, highlighting the importance of the early phase post-cessation of ovarian function. E2 replacement therapy, even if it was not immediately initiated after OVX, reversed these unfavorable changes and upregulated cardiac miRNA-26a, previously unknown to be affected by menopausal status.
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Affiliation(s)
- Elishai Assayag
- Department of Endocrinology and Metabolism, Division of Medicine, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel; (E.A.); (I.G.); (E.C.-K.)
| | - Irina Gurt
- Department of Endocrinology and Metabolism, Division of Medicine, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel; (E.A.); (I.G.); (E.C.-K.)
| | - Einav Cohen-Kfir
- Department of Endocrinology and Metabolism, Division of Medicine, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel; (E.A.); (I.G.); (E.C.-K.)
| | - Joshua Stokar
- Department of Endocrinology and Metabolism, Division of Medicine, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel; (E.A.); (I.G.); (E.C.-K.)
| | - Donna R. Zwas
- Linda Joy Pollin Cardiovascular Wellness Center for Women, Division of Cardiology, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel;
| | - Rivka Dresner-Pollak
- Department of Endocrinology and Metabolism, Division of Medicine, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel; (E.A.); (I.G.); (E.C.-K.)
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Improta-Caria AC, Rodrigues LF, Joaquim VHA, De Sousa RAL, Fernandes T, Oliveira EM. MicroRNAs regulating signaling pathways in cardiac fibrosis: potential role of the exercise training. Am J Physiol Heart Circ Physiol 2024; 326:H497-H510. [PMID: 38063810 PMCID: PMC11219062 DOI: 10.1152/ajpheart.00410.2023] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 12/05/2023] [Accepted: 12/05/2023] [Indexed: 02/09/2024]
Abstract
Cardiovascular and metabolic diseases such as hypertension, type 2 diabetes, and obesity develop long-term fibrotic processes in the heart, promoting pathological cardiac remodeling, including after myocardial infarction, reparative fibrotic processes also occur. These processes are regulated by many intracellular signaling pathways that have not yet been completely elucidated, including those associated with microRNA (miRNA) expression. miRNAs are small RNA transcripts (18-25 nucleotides in length) that act as posttranscriptionally regulators of gene expression, inhibiting or degrading one or more target messenger RNAs (mRNAs), and proven to be involved in many biological processes such as cell cycle, differentiation, proliferation, migration, and apoptosis, directly affecting the pathophysiology of several diseases, including cardiac fibrosis. Exercise training can modulate the expression of miRNAs and it is known to be beneficial in various cardiovascular diseases, attenuating cardiac fibrosis processes. However, the signaling pathways modulated by the exercise associated with miRNAs in cardiac fibrosis were not fully understood. Thus, this review aims to analyze the expression of miRNAs that modulate signaling pathways in cardiac fibrosis processes that can be regulated by exercise training.
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Affiliation(s)
- Alex Cleber Improta-Caria
- Laboratory of Biochemistry and Molecular Biology of the Exercise, Physical Education and Sport School, University of São Paulo, São Paulo, Brazil
| | - Luis Felipe Rodrigues
- Laboratory of Biochemistry and Molecular Biology of the Exercise, Physical Education and Sport School, University of São Paulo, São Paulo, Brazil
| | - Victor Hugo Antonio Joaquim
- Laboratory of Biochemistry and Molecular Biology of the Exercise, Physical Education and Sport School, University of São Paulo, São Paulo, Brazil
| | | | - Tiago Fernandes
- Laboratory of Biochemistry and Molecular Biology of the Exercise, Physical Education and Sport School, University of São Paulo, São Paulo, Brazil
| | - Edilamar Menezes Oliveira
- Laboratory of Biochemistry and Molecular Biology of the Exercise, Physical Education and Sport School, University of São Paulo, São Paulo, Brazil
- Departments of Internal Medicine, Center for Regenerative Medicine, USF Health Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States
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21
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Li X, Sun M, Wang Z, Sun S, Wang Y. Recent advances in mechanistic studies of heart failure with preserved ejection fraction and its comorbidities-Role of microRNAs. Eur J Clin Invest 2024; 54:e14130. [PMID: 38071416 DOI: 10.1111/eci.14130] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 10/22/2023] [Accepted: 11/11/2023] [Indexed: 02/15/2024]
Abstract
BACKGROUND Heart failure with preserved ejection fraction (HFpEF) is a multifaceted syndrome with a complex aetiology commonly associated with comorbidities such as diabetes mellitus, obesity, hypertension and renal disease. Various diseases induce systemic, chronic and low-grade inflammation; microvascular dysfunction; metabolic stress; tissue ischemia; and fibrosis, leading to HFpEF. An effective treatment for HFpEF is lacking, largely owing to its pathophysiological heterogeneity. Recent studies have revealed that microRNAs (miRNAs) play crucial roles in regulating the pathogenesis of HFpEF and its comorbidities. METHODS This narrative review included original articles and reviews published over the past 20 years found through 'PubMed' and 'Web of Science'. The search terms included "HFpEF," "MicroRNAs," "comorbidities," "Microvascular Dysfunction (MVD)," "inflammation," "pathophysiology," "endothelial dysfunction," "energy metabolism abnormalities" "cardiac fibrosis" and "treatment." RESULTS Inflammation, MVD, abnormal energy metabolism, myocardial hypertrophy and myocardial fibrosis are important pathophysiological mechanisms underlying HFpEF. As gene expression regulators, miRNAs may contribute to the pathophysiology of HFpEF and are expected to serve in the stratification of patients with HFpEF and as prognostic indicators for monitoring treatment responses. CONCLUSIONS A customized strategy based on miRNAs has emerged as an effective treatment for HFpEF. In this review, we discuss recent research surrounding miRNAs and HFpEF and propose potential miRNA targets for the pathophysiology of HFpEF and its comorbidities. Although current research concerning miRNAs and their therapeutic potential is in its early stages, miRNA-based diagnostics and therapeutics hold great promise in the future.
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Affiliation(s)
- Xiaonan Li
- Department of Geriatrics, Jilin Geriatrics Clinical Research Center, The First Hospital of Jilin University, Changchun, China
| | - Min Sun
- Department of Geriatrics, Jilin Geriatrics Clinical Research Center, The First Hospital of Jilin University, Changchun, China
| | - Zhe Wang
- Department of Geriatrics, Jilin Geriatrics Clinical Research Center, The First Hospital of Jilin University, Changchun, China
| | - Siming Sun
- Department of Clinical Research, The First Hospital of Jilin University, Changchun, China
| | - Yuehui Wang
- Department of Geriatrics, Jilin Geriatrics Clinical Research Center, The First Hospital of Jilin University, Changchun, China
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22
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Lozano-Velasco E, Inácio JM, Sousa I, Guimarães AR, Franco D, Moura G, Belo JA. miRNAs in Heart Development and Disease. Int J Mol Sci 2024; 25:1673. [PMID: 38338950 PMCID: PMC10855082 DOI: 10.3390/ijms25031673] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 01/25/2024] [Accepted: 01/27/2024] [Indexed: 02/12/2024] Open
Abstract
Cardiovascular diseases (CVD) are a group of disorders that affect the heart and blood vessels. They include conditions such as myocardial infarction, coronary artery disease, heart failure, arrhythmia, and congenital heart defects. CVDs are the leading cause of death worldwide. Therefore, new medical interventions that aim to prevent, treat, or manage CVDs are of prime importance. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the posttranscriptional level and play important roles in various biological processes, including cardiac development, function, and disease. Moreover, miRNAs can also act as biomarkers and therapeutic targets. In order to identify and characterize miRNAs and their target genes, scientists take advantage of computational tools such as bioinformatic algorithms, which can also assist in analyzing miRNA expression profiles, functions, and interactions in different cardiac conditions. Indeed, the combination of miRNA research and bioinformatic algorithms has opened new avenues for understanding and treating CVDs. In this review, we summarize the current knowledge on the roles of miRNAs in cardiac development and CVDs, discuss the challenges and opportunities, and provide some examples of recent bioinformatics for miRNA research in cardiovascular biology and medicine.
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Affiliation(s)
- Estefania Lozano-Velasco
- Cardiovascular Development Group, Department of Experimental Biology, University of Jaen, 23071 Jaen, Spain; (E.L.-V.); (D.F.)
| | - José Manuel Inácio
- Stem Cells and Development Laboratory, iNOVA4Health, NOVA Medical School|Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-082 Lisbon, Portugal;
| | - Inês Sousa
- Genome Medicine Lab, Department of Medical Sciences, Institute for Biomedicine–iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal; (I.S.); (A.R.G.); (G.M.)
| | - Ana Rita Guimarães
- Genome Medicine Lab, Department of Medical Sciences, Institute for Biomedicine–iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal; (I.S.); (A.R.G.); (G.M.)
| | - Diego Franco
- Cardiovascular Development Group, Department of Experimental Biology, University of Jaen, 23071 Jaen, Spain; (E.L.-V.); (D.F.)
| | - Gabriela Moura
- Genome Medicine Lab, Department of Medical Sciences, Institute for Biomedicine–iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal; (I.S.); (A.R.G.); (G.M.)
| | - José António Belo
- Stem Cells and Development Laboratory, iNOVA4Health, NOVA Medical School|Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1150-082 Lisbon, Portugal;
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23
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Liu N, Zhen Z, Xiong X, Xue Y. Aerobic exercise protects MI heart through miR-133a-3p downregulation of connective tissue growth factor. PLoS One 2024; 19:e0296430. [PMID: 38271362 PMCID: PMC10810442 DOI: 10.1371/journal.pone.0296430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 12/11/2023] [Indexed: 01/27/2024] Open
Abstract
OBJECTIVE To investigate the effect of aerobic exercise intervention to inhibit cardiomyocyte apoptosis and thus improve cardiac function in myocardial infarction (MI) mice by regulating CTGF expression through miR-133a-3p. METHODS Male C57/BL6 mice, 7-8 weeks old, were randomly divided into sham-operated group (S group), sham-operated +aerobic exercise group (SE group), myocardial infarction group (MI group) and MI + aerobic exercise group (ME group). The mice were anesthetized the day after training and cardiac function was assessed by cardiac echocardiography. Myocardial collagen volume fraction (CVF%) was analyzed by Masson staining. Myocardial CTGF, Bax and Bcl-2 were detected by Western blotting, and myocardial miR-133a-3p was measured by RT-qPCR. RESULTS Compared with the S group, miR-133a-3p, Bcl-2 and EF were significantly decreased and CTGF, Bax, Bax/ Bcl-2, Caspase 3, Cleaved Caspase-3, LVIDd, LVIDs and CVF were significantly increased in the MI group. Compared with the MI group, miR-133a-3p, Bcl-2 and EF were significantly increased, cardiac function was significantly improved, and CTGF, Bax, Bax/ Bcl-2, Caspase 3, Cleaved Caspase-3, LVIDd, LVIDs and CVF were significantly decreased in ME group. The miR-133a-3p was significantly lower and CTGF was significantly higher in the H2O2 intervention group compared with the control group of H9C2 rat cardiomyocytes. miR-133a-3p was significantly higher and CTGF was significantly lower in the AICAR intervention group compared to the H2O2 intervention group. Compared with the control group of H9C2 rat cardiomyocytes, CTGF, Bax and Bax/Bcl-2 were significantly increased and Bcl-2 was significantly decreased in the miR-133a-3p inhibitor intervention group; CTGF, Bax and Bax/Bcl-2 were significantly decreased and Bcl-2 was significantly upregulated in the miR-133a-3p mimics intervention group. CONCLUSION Aerobic exercise down-regulated CTGF expression in MI mouse myocardium through miR-133a-3p, thereby inhibiting cardiomyocyte apoptosis and improving cardiac function.
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Affiliation(s)
- Niu Liu
- College of P.E, Beijing Normal University, Beijing, China
- School of Physical Education, Weinan Normal University, Weinan, Shaanxi, China
| | - Zhiping Zhen
- College of P.E, Beijing Normal University, Beijing, China
| | - Xin Xiong
- College of P.E, Beijing Normal University, Beijing, China
| | - Yaqi Xue
- College of P.E, Beijing Normal University, Beijing, China
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24
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Gocer Z, Elek A, Caska H, Bozgeyik I. MicroRNAs and cardiac fibrosis: A comprehensive update on mechanisms and consequences. Pathol Res Pract 2023; 251:154853. [PMID: 37857035 DOI: 10.1016/j.prp.2023.154853] [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: 08/23/2023] [Revised: 09/30/2023] [Accepted: 10/02/2023] [Indexed: 10/21/2023]
Abstract
Fibrosis is a pathological wound-healing mechanism that results by the overactivation of fibroblasts. Fibrosis can become obstructive and deleterious during regeneration of various body tissues including cardiac muscle. This ultimately results in the development of cardiac fibrosis, characterized by an excessive buildup of extracellular matrix proteins. Thus, it could lead to arrhythmias and heart failure which creates a leading public health burden worldwide. MiRNAs are small non-coding RNAs with great potential for diagnostic and therapeutic purposes. Mounting evidence indicates that miRNAs are involved in the deregulation of tissue homeostasis during myocardial fibrosis. For instance, miRNAs that are implicated in the regulation of TGF-beta signaling pathway have been reported to be significantly altered in myocardial fibrosis. Accordingly, in this comprehensive review, we discuss and highlight recent available data on the role of miRNAs during myocardial fibrosis, providing valuable insights into the miRNA modulation of cardiac fibrosis and miRNAs targets that can be used in the future therapeutic interventions to cardiac fibrosis.
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Affiliation(s)
- Zekihan Gocer
- Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Alperen Elek
- Faculty of Medicine, Ege University, Izmir, Turkey
| | - Halil Caska
- Department of Medical Biology and Genetics, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey
| | - Ibrahim Bozgeyik
- Department of Medical Biology, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey.
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25
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Akhtar MS, Alavudeen SS, Raza A, Imam MT, Almalki ZS, Tabassum F, Iqbal MJ. Current understanding of structural and molecular changes in diabetic cardiomyopathy. Life Sci 2023; 332:122087. [PMID: 37714373 DOI: 10.1016/j.lfs.2023.122087] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 09/11/2023] [Accepted: 09/12/2023] [Indexed: 09/17/2023]
Abstract
Diabetic Mellitus has been characterized as the most prevalent disease throughout the globe associated with the serious morbidity and mortality of vital organs. Cardiomyopathy is the major leading complication of diabetes and within this, myocardial dysfunction or failure is the leading cause of the emergency hospital admission. The review is aimed to comprehend the perspectives associated with diabetes-induced cardiovascular complications. The data was collected from several electronic databases such as Google Scholar, Science Direct, ACS publication, PubMed, Springer, etc. using the keywords such as diabetes and its associated complication, the prevalence of diabetes, the anatomical and physiological mechanism of diabetes-induced cardiomyopathy, the molecular mechanism of diabetes-induced cardiomyopathy, oxidative stress, and inflammatory stress, etc. The collected scientific data was screened by different experts based on the inclusion and exclusion criteria of the study. This review findings revealed that diabetes is associated with inefficient substrate utilization, inability to increase glucose metabolism and advanced glycation end products within the diabetic heart resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity, and initially subclinical cardiac dysfunction and finally in overt heart failure. Furthermore, several factors such as hypertension, overexpression of renin angiotensin system, hypertrophic obesity, etc. have been seen as majorly associated with cardiomyopathy. The molecular examination showed biochemical disability and generation of the varieties of free radicals and inflammatory cytokines and becomes are the substantial causes of cardiomyopathy. This review provides a better understanding of the involved pathophysiology and offers an open platform for discussing and targeting therapy in alleviating diabetes-induced early heart failure or cardiomyopathy.
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Affiliation(s)
- Md Sayeed Akhtar
- Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Al-Fara, Abha 62223, Saudi Arabia.
| | - Sirajudeen S Alavudeen
- Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Al-Fara, Abha 62223, Saudi Arabia
| | - Asif Raza
- Department of Pharmacology, Penn State Cancer Institute, CH72, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, USA
| | - Mohammad Tarique Imam
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 16273, Saudi Arabia
| | - Ziad Saeed Almalki
- Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 16273, Saudi Arabia
| | - Fauzia Tabassum
- Department of Pharmacology, College of Dentistry and Pharmacy, Buraydah Private College, Al Qassim 51418, Saudi Arabia; Department of Pharmacology, Vision College, Ishbilia, Riyadh 13226-3830, Saudi Arabia
| | - Mir Javid Iqbal
- Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA
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26
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Yu X. Promising Therapeutic Treatments for Cardiac Fibrosis: Herbal Plants and Their Extracts. Cardiol Ther 2023; 12:415-443. [PMID: 37247171 PMCID: PMC10423196 DOI: 10.1007/s40119-023-00319-4] [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: 02/28/2023] [Accepted: 04/27/2023] [Indexed: 05/30/2023] Open
Abstract
Cardiac fibrosis is closely associated with multiple heart diseases, which are a prominent health issue in the global world. Neurohormones and cytokines play indispensable roles in cardiac fibrosis. Many signaling pathways participate in cardiac fibrosis as well. Cardiac fibrosis is due to impaired degradation of collagen and impaired fibroblast activation, and collagen accumulation results in increasing heart stiffness and inharmonious activity, leading to structure alterations and finally cardiac function decline. Herbal plants have been applied in traditional medicines for thousands of years. Because of their naturality, they have attracted much attention for use in resisting cardiac fibrosis in recent years. This review sheds light on several extracts from herbal plants, which are promising therapeutics for reversing cardiac fibrosis.
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Affiliation(s)
- Xuejing Yu
- Department of Internal Medicine, Division of Cardiology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75235, USA.
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27
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Gluba-Sagr A, Franczyk B, Rysz-Górzyńska M, Ławiński J, Rysz J. The Role of miRNA in Renal Fibrosis Leading to Chronic Kidney Disease. Biomedicines 2023; 11:2358. [PMID: 37760798 PMCID: PMC10525803 DOI: 10.3390/biomedicines11092358] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 08/14/2023] [Accepted: 08/19/2023] [Indexed: 09/29/2023] Open
Abstract
Chronic kidney disease (CKD) is an important health concern that is expected to be the fifth most widespread cause of death worldwide by 2040. The presence of chronic inflammation, oxidative stress, ischemia, etc., stimulates the development and progression of CKD. Tubulointerstitial fibrosis is a common pathomechanism of renal dysfunction, irrespective of the primary origin of renal injury. With time, fibrosis leads to end-stage renal disease (ESRD). Many studies have demonstrated that microRNAs (miRNAs, miRs) are involved in the onset and development of fibrosis and CKD. miRNAs are vital regulators of some pathophysiological processes; therefore, their utility as therapeutic agents in various diseases has been suggested. Several miRNAs were demonstrated to participate in the development and progression of kidney disease. Since renal fibrosis is an important problem in chronic kidney disease, many scientists have focused on the determination of miRNAs associated with kidney fibrosis. In this review, we present the role of several miRNAs in renal fibrosis and the potential pathways involved. However, as well as those mentioned above, other miRs have also been suggested to play a role in this process in CKD. The reports concerning the impact of some miRNAs on fibrosis are conflicting, probably because the expression and regulation of miRNAs occur in a tissue- and even cell-dependent manner. Moreover, different assessment modes and populations have been used. There is a need for large studies and clinical trials to confirm the role of miRs in a clinical setting. miRNAs have great potential; thus, their analysis may improve diagnostic and therapeutic strategies.
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Affiliation(s)
- Anna Gluba-Sagr
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland
| | - Beata Franczyk
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland
| | - Magdalena Rysz-Górzyńska
- Department of Ophthalmology and Visual Rehabilitation, Medical University of Lodz, 90-549 Lodz, Poland
| | - Janusz Ławiński
- Department of Urology, Institute of Medical Sciences, College of Medical Sciences, University of Rzeszow, 35-055 Rzeszow, Poland
| | - Jacek Rysz
- Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland
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28
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Chimenti C, Magnocavallo M, Vetta G, Alfarano M, Manguso G, Ajmone F, Ballatore F, Costantino J, Ciaramella P, Severino P, Miraldi F, Lavalle C, Vizza CD. The Role of MicroRNA in the Myocarditis: a Small Actor for a Great Role. Curr Cardiol Rep 2023:10.1007/s11886-023-01888-5. [PMID: 37269474 DOI: 10.1007/s11886-023-01888-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/24/2023] [Indexed: 06/05/2023]
Abstract
PURPOSE OF REVIEW Myocarditis is an inflammation of the myocardium secondary to a variety of agents such as infectious pathogens, toxins, drugs, and autoimmune disorders. In our review, we provide an overview of miRNA biogenesis and their role in the etiology and pathogenesis of myocarditis, evaluating future directions for myocarditis management. RECENT FINDINGS Advances in genetic manipulation techniques allowed to demonstrate the important role of RNA fragments, especially microRNAs (miRNAs), in cardiovascular pathogenesis. miRNAs are small non-coding RNA molecules that regulate the post-transcriptional gene expression. Advances in molecular techniques allowed to identify miRNA's role in pathogenesis of myocarditis. miRNAs are related to viral infection, inflammation, fibrosis, and apoptosis of cardiomyocytes, making them not only promising diagnostic markers but also prognostics and therapeutic targets in myocarditis. Of course, further real-world studies will be needed to assess the diagnostic accuracy and applicability of miRNA in the myocarditis diagnosis.
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Affiliation(s)
- Cristina Chimenti
- Clinical, Anestesiologic and Cardiovascular Sciences, La Sapienza University of Rome, Rome, Italy.
| | - Michele Magnocavallo
- Cardiology Division, Arrhythmology Unit, S. Giovanni Calibita Hospital, Isola Tiberina, Rome, Italy
| | - Giampaolo Vetta
- Department of Clinical and Experimental Medicine, Cardiology Unit, University of Messina, Mesina, Italy
| | - Maria Alfarano
- Clinical, Anestesiologic and Cardiovascular Sciences, La Sapienza University of Rome, Rome, Italy
| | - Giulia Manguso
- Clinical, Anestesiologic and Cardiovascular Sciences, La Sapienza University of Rome, Rome, Italy
| | - Francesco Ajmone
- Clinical, Anestesiologic and Cardiovascular Sciences, La Sapienza University of Rome, Rome, Italy
| | - Federico Ballatore
- Clinical, Anestesiologic and Cardiovascular Sciences, La Sapienza University of Rome, Rome, Italy
| | - Jacopo Costantino
- Clinical, Anestesiologic and Cardiovascular Sciences, La Sapienza University of Rome, Rome, Italy
| | - Piera Ciaramella
- Clinical, Anestesiologic and Cardiovascular Sciences, La Sapienza University of Rome, Rome, Italy
| | - Paolo Severino
- Clinical, Anestesiologic and Cardiovascular Sciences, La Sapienza University of Rome, Rome, Italy
| | - Fabio Miraldi
- Clinical, Anestesiologic and Cardiovascular Sciences, La Sapienza University of Rome, Rome, Italy
| | - Carlo Lavalle
- Clinical, Anestesiologic and Cardiovascular Sciences, La Sapienza University of Rome, Rome, Italy
| | - Carmine Dario Vizza
- Clinical, Anestesiologic and Cardiovascular Sciences, La Sapienza University of Rome, Rome, Italy
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Pérez-Cremades D, Chen J, Assa C, Feinberg MW. MicroRNA-mediated control of myocardial infarction in diabetes. Trends Cardiovasc Med 2023; 33:195-201. [PMID: 35051592 PMCID: PMC9288556 DOI: 10.1016/j.tcm.2022.01.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 01/11/2022] [Accepted: 01/11/2022] [Indexed: 12/16/2022]
Abstract
Diabetes mellitus is a global public health problem whose cases will continue to rise along with the progressive increase in obesity and the aging of the population. People with diabetes exhibit higher risk of cardiovascular complications, especially myocardial infarction (MI). microRNAs (miRNAs) are evolutionary conserved small non-coding RNAs involved in the regulation of biological processes by interfering in gene expression at the post-transcriptional level. Accumulating studies in the last two decades have uncovered the role of stage-specific miRNAs associated with key pathobiological events observed in the hearts of people with diabetes and MI, including cardiomyocyte death, angiogenesis, inflammatory response, myocardial remodeling, and myocardial lipotoxicity. A better understanding of the importance of these miRNAs and their targets may provide novel opportunities for RNA-based therapeutic interventions to address the increased risk of MI in diabetes.
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Affiliation(s)
- Daniel Pérez-Cremades
- Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA 02115; Department of Physiology, University of Valencia and INCLIVA Biomedical Research Institute, Valencia, Spain 46010
| | - Jingshu Chen
- Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA 02115
| | - Carmel Assa
- Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA 02115
| | - Mark W Feinberg
- Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA 02115.
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30
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Chen S, Huang Y, Liu R, Lin Z, Huang B, Ai W, He J, Gao Y, Xie P. Exosomal miR‑152‑5p/ARHGAP6/ROCK axis regulates apoptosis and fibrosis in cardiomyocytes. Exp Ther Med 2023; 25:165. [PMID: 36936709 PMCID: PMC10015317 DOI: 10.3892/etm.2023.11864] [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: 11/02/2022] [Accepted: 02/08/2023] [Indexed: 03/04/2023] Open
Abstract
Acute myocardial infarction (AMI) is a fatal cardiovascular disease with a high mortality rate. The discovery of effective biomarkers is crucial for the diagnosis and treatment of AMI. In the present study, miRNA sequencing and reverse transcription-quantitative polymerase chain reaction techniques revealed that the expression of exosome derived miR-152-5p was significantly downregulated in patients with AMI compared with healthy controls. A series of functional validation experiments were then performed using H9c2 cardiomyocytes. Following transfection of the cardiomyocytes using an miR-152-5p inhibitor, immunofluorescence staining of a-smooth muscle actin revealed a marked increase in fibrosis. Western blotting revealed that the expression levels of the apoptotic protein Bax, TNF-α and collagen-associated proteins were significantly increased, whereas those of the apoptosis-inhibiting factor Bcl-2 and vascular endothelial growth factor A were significantly decreased. Furthermore, the binding of Rho GTPase-activating protein 6 (ARHGAP6) to miR-152-5p was predicted using an online database and verified using a dual-luciferase reporter gene assay. The transfection of cardiomyocytes with miR-152-5p mimics was found to inhibit the activation of ARHGAP6 and Rho-associated coiled-coil containing kinase 2 (ROCK2). These results suggest that miR-152-5p targets ARHGAP6 through the ROCK signaling pathway to inhibit AMI, which implies that miR-152-5p may be a diagnostic indicator and potential target for treatment of myocardial infarction.
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Affiliation(s)
- Shaoyuan Chen
- Department of Cardiology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong 518052, P.R. China
- Department of Cardiology, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong 518060, P.R. China
- Correspondence to: Dr Shaoyuan Chen, Department of Cardiology, Huazhong University of Science and Technology Union Shenzhen Hospital, 89 Taoyuan Road, Nanshan, Shenzhen, Guangdong 518052, P.R. China
| | - Yulang Huang
- Department of Cardiology, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, Guangdong 518067, P.R. China
| | - Rongzhi Liu
- Department of Cardiology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong 518052, P.R. China
| | - Zixiang Lin
- Department of Cardiology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong 518052, P.R. China
| | - Bihan Huang
- Department of Cardiology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong 518052, P.R. China
| | - Wen Ai
- Department of Cardiology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong 518052, P.R. China
- Department of Cardiology, The 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, Guangdong 518060, P.R. China
| | - Jianjun He
- First Clinical Department, Guangdong Medical University, Zhanjiang, Guangdong 524002, P.R. China
| | - Yulan Gao
- Department of Cardiology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong 518052, P.R. China
| | - Peiyi Xie
- Department of Cardiology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong 518052, P.R. China
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31
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The Role of ncRNAs in Cardiac Infarction and Regeneration. J Cardiovasc Dev Dis 2023; 10:jcdd10030123. [PMID: 36975887 PMCID: PMC10052289 DOI: 10.3390/jcdd10030123] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 03/06/2023] [Accepted: 03/13/2023] [Indexed: 03/17/2023] Open
Abstract
Myocardial infarction is the most prevalent cardiovascular disease worldwide, and it is defined as cardiomyocyte cell death due to a lack of oxygen supply. Such a temporary absence of oxygen supply, or ischemia, leads to extensive cardiomyocyte cell death in the affected myocardium. Notably, reactive oxygen species are generated during the reperfusion process, driving a novel wave of cell death. Consequently, the inflammatory process starts, followed by fibrotic scar formation. Limiting inflammation and resolving the fibrotic scar are essential biological processes with respect to providing a favorable environment for cardiac regeneration that is only achieved in a limited number of species. Distinct inductive signals and transcriptional regulatory factors are key components that modulate cardiac injury and regeneration. Over the last decade, the impact of non-coding RNAs has begun to be addressed in many cellular and pathological processes including myocardial infarction and regeneration. Herein, we provide a state-of-the-art review of the current functional role of diverse non-coding RNAs, particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in different biological processes involved in cardiac injury as well as in distinct experimental models of cardiac regeneration.
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32
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van Nieuwenhoven FA, Schroen B, Barile L, van Middendorp L, Prinzen FW, Auricchio A. Plasma Extracellular Vesicles as Liquid Biopsy to Unravel the Molecular Mechanisms of Cardiac Reverse Remodeling Following Resynchronization Therapy? J Clin Med 2023; 12:jcm12020665. [PMID: 36675594 PMCID: PMC9862724 DOI: 10.3390/jcm12020665] [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: 11/01/2022] [Revised: 01/10/2023] [Accepted: 01/12/2023] [Indexed: 01/18/2023] Open
Abstract
Cardiac resynchronization therapy (CRT) has become a valuable addition to the treatment options for heart failure, in particular for patients with disturbances in electrical conduction that lead to regionally different contraction patterns (dyssynchrony). Dyssynchronous hearts show extensive molecular and cellular remodeling, which has primarily been investigated in experimental animals. Evidence showing that at least several miRNAs play a role in this remodeling is increasing. A comparison of results from measurements in plasma and myocardial tissue suggests that plasma levels of miRNAs may reflect the expression of these miRNAs in the heart. Because many miRNAs released in the plasma are included in extracellular vesicles (EVs), which protect them from degradation, measurement of myocardium-derived miRNAs in peripheral blood EVs may open new avenues to investigate and monitor (reverse) remodeling in dyssynchronous and resynchronized hearts of patients.
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Affiliation(s)
- Frans A. van Nieuwenhoven
- Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, 6200 MD Maastricht, The Netherlands
| | - Blanche Schroen
- Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University, 6200 MD Maastricht, The Netherlands
| | - Lucio Barile
- Laboratory for Cardiovascular Theranostics, Istituto Cardiocentro Ticino, 6900 Lugano, Switzerland
| | - Lars van Middendorp
- Department of Cardiothoracic Surgery, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands
| | - Frits W. Prinzen
- Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, 6200 MD Maastricht, The Netherlands
- Correspondence:
| | - Angelo Auricchio
- Department of Cardiology, Istituto Cardiocentro Ticino, Ente Ospedaliero Cantonale, 6900 Lugano, Switzerland
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33
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Yaghobi R, Afshari A, Roozbeh J. Host and viral
RNA
dysregulation during
BK
polyomavirus
infection in kidney transplant recipients. WIRES RNA 2022:e1769. [DOI: 10.1002/wrna.1769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 11/12/2022] [Accepted: 11/14/2022] [Indexed: 12/12/2022]
Affiliation(s)
- Ramin Yaghobi
- Shiraz Transplant Research Center Shiraz University of Medical Sciences Shiraz Iran
| | - Afsoon Afshari
- Shiraz Nephro‐Urology Research Center Shiraz University of Medical Sciences Shiraz Iran
| | - Jamshid Roozbeh
- Shiraz Nephro‐Urology Research Center Shiraz University of Medical Sciences Shiraz Iran
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34
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Du Y, Wu T. Heart failure and cancer: From active exposure to passive adaption. Front Cardiovasc Med 2022; 9:992011. [PMID: 36304546 PMCID: PMC9592839 DOI: 10.3389/fcvm.2022.992011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 09/20/2022] [Indexed: 12/06/2022] Open
Abstract
The human body seems like a "balance integrator." On the one hand, the body constantly actively receives various outside stimuli and signals to induce changes. On the other hand, several internal regulations would be initiated to adapt to these changes. In most cases, the body could keep the balance in vitro and in vivo to reach a healthy body. However, in some cases, the body can only get to a pathological balance. Actively exposed to unhealthy lifestyles and passively adapting to individual primary diseases lead to a similarly inner environment for both heart failure and cancer. To cope with these stimuli, the body must activate the system regulation mechanism and face the mutual interference. This review summarized the association between heart failure and cancer from active exposure to passive adaption. Moreover, we hope to inspire researchers to contemplate these two diseases from the angle of overall body consideration.
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Affiliation(s)
- Yantao Du
- Ningbo Institute of Medical Science, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang, China
| | - Tao Wu
- Department of Cardiovascular Center, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang, China
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35
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Reis-Ferreira A, Neto-Mendes J, Brás-Silva C, Lobo L, Fontes-Sousa AP. Emerging Roles of Micrornas in Veterinary Cardiology. Vet Sci 2022; 9:533. [PMID: 36288146 PMCID: PMC9607079 DOI: 10.3390/vetsci9100533] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 09/15/2022] [Accepted: 09/20/2022] [Indexed: 11/29/2022] Open
Abstract
Over the last years, the importance of microRNAs (miRNAs) has increasingly been recognised. Each miRNA is a short sequence of non-coding RNA that influences countless genes' expression and, thereby, contributes to several physiological pathways and diseases. It has been demonstrated that miRNAs participate in the development of many cardiovascular diseases (CVDs). This review synopsises the most recent studies emphasising miRNA's influence in several CVDs affecting dogs and cats. It provides a concise outline of miRNA's biology and function, the diagnostic potential of circulating miRNAs as biomarkers, and their role in different CVDs. It also discusses known and future roles for miRNAs as potential clinical biomarkers and therapeutic targets. So, this review gives a comprehensive outline of the most relevant miRNAs related to CVDs in Veterinary Medicine.
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Affiliation(s)
- Ana Reis-Ferreira
- Hospital Veterinário do Porto, Travessa Silva Porto 174, 4250-475 Porto, Portugal
- ICBAS-UP, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal
| | - Joana Neto-Mendes
- ICBAS-UP, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal
| | - Carmen Brás-Silva
- UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal
| | - Luís Lobo
- Hospital Veterinário do Porto, Travessa Silva Porto 174, 4250-475 Porto, Portugal
- Faculdade de Medicina Veterinária, Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal
- Centro de Estudos de Ciência Animal, Campus Agrário de Vairão, 4480-009 Vila do Conde, Portugal
| | - Ana Patrícia Fontes-Sousa
- ICBAS-UP, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal
- Departamento de Imuno-Fisiologia e Farmacologia, Centro de Investigação Farmacológica e Inovação Medicamentosa (MedInUP), Universidade do Porto, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Rua Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal
- UPVET, Hospital Veterinário da Universidade do Porto, Rua Jorge de Viterbo Ferreira 132, 4050-313 Porto, Portugal
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36
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Molecular Approaches and Echocardiographic Deformation Imaging in Detecting Myocardial Fibrosis. Int J Mol Sci 2022; 23:ijms231810944. [PMID: 36142856 PMCID: PMC9501415 DOI: 10.3390/ijms231810944] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Revised: 09/11/2022] [Accepted: 09/16/2022] [Indexed: 12/25/2022] Open
Abstract
The pathological remodeling of myocardial tissue is the main cause of heart diseases. Several processes are involved in the onset of heart failure, and the comprehension of the mechanisms underlying the pathological phenotype deserves special attention to find novel procedures to identify the site of injury and develop novel strategies, as well as molecular druggable pathways, to counteract the high degree of morbidity associated with it. Myocardial fibrosis (MF) is recognized as a critical trigger for disruption of heart functionality due to the excessive accumulation of extracellular matrix proteins, in response to an injury. Its diagnosis remains focalized on invasive techniques, such as endomyocardial biopsy (EMB), or may be noninvasively detected by cardiac magnetic resonance imaging (CMRI). The detection of MF by non-canonical markers remains a challenge in clinical practice. During the last two decades, two-dimensional (2D) speckle tracking echocardiography (STE) has emerged as a new non-invasive imaging modality, able to detect myocardial tissue abnormalities without specifying the causes of the underlying histopathological changes. In this review, we highlighted the clinical utility of 2D-STE deformation imaging for tissue characterization, and its main technical limitations and criticisms. Moreover, we focalized on the importance of coupling 2D-STE examination with the molecular approaches in the clinical decision-making processes, in particular when the 2D-STE does not reflect myocardial dysfunction directly. We also attempted to examine the roles of epigenetic markers of MF and hypothesized microRNA-based mechanisms aiming to understand how they match with the clinical utility of echocardiographic deformation imaging for tissue characterization and MF assessment.
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Cardiovascular Disease-Associated MicroRNAs as Novel Biomarkers of First-Trimester Screening for Gestational Diabetes Mellitus in the Absence of Other Pregnancy-Related Complications. Int J Mol Sci 2022; 23:ijms231810635. [PMID: 36142536 PMCID: PMC9501303 DOI: 10.3390/ijms231810635] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 09/08/2022] [Accepted: 09/09/2022] [Indexed: 11/25/2022] Open
Abstract
We assessed the diagnostic potential of cardiovascular disease-associated microRNAs for the early prediction of gestational diabetes mellitus (GDM) in singleton pregnancies of Caucasian descent in the absence of other pregnancy-related complications. Whole peripheral venous blood samples were collected within 10 to 13 weeks of gestation. This retrospective study involved all pregnancies diagnosed with only GDM (n = 121) and 80 normal term pregnancies selected with regard to equality of sample storage time. Gene expression of 29 microRNAs was assessed using real-time RT-PCR. Upregulation of 11 microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-23a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-181a-5p, miR-195-5p, miR-499a-5p, and miR-574-3p) was observed in pregnancies destinated to develop GDM. Combined screening of all 11 dysregulated microRNAs showed the highest accuracy for the early identification of pregnancies destinated to develop GDM. This screening identified 47.93% of GDM pregnancies at a 10.0% false positive rate (FPR). The predictive model for GDM based on aberrant microRNA expression profile was further improved via the implementation of clinical characteristics (maternal age and BMI at early stages of gestation and an infertility treatment by assisted reproductive technology). Following this, 69.17% of GDM pregnancies were identified at a 10.0% FPR. The effective prediction model specifically for severe GDM requiring administration of therapy involved using a combination of these three clinical characteristics and three microRNA biomarkers (miR-20a-5p, miR-20b-5p, and miR-195-5p). This model identified 78.95% of cases at a 10.0% FPR. The effective prediction model for GDM managed by diet only required the involvement of these three clinical characteristics and eight microRNA biomarkers (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-100-5p, miR-125b-5p, miR-195-5p, miR-499a-5p, and miR-574-3p). With this, the model identified 50.50% of GDM pregnancies managed by diet only at a 10.0% FPR. When other clinical variables such as history of miscarriage, the presence of trombophilic gene mutations, positive first-trimester screening for preeclampsia and/or fetal growth restriction by the Fetal Medicine Foundation algorithm, and family history of diabetes mellitus in first-degree relatives were included in the GDM prediction model, the predictive power was further increased at a 10.0% FPR (72.50% GDM in total, 89.47% GDM requiring therapy, and 56.44% GDM managed by diet only). Cardiovascular disease-associated microRNAs represent promising early biomarkers to be implemented into routine first-trimester screening programs with a very good predictive potential for GDM.
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38
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Rashidmayvan M, Sahebi R, Ghayour-Mobarhan M. Long non-coding RNAs: a valuable biomarker for metabolic syndrome. Mol Genet Genomics 2022; 297:1169-1183. [PMID: 35854006 DOI: 10.1007/s00438-022-01922-1] [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: 03/27/2022] [Accepted: 06/25/2022] [Indexed: 10/17/2022]
Abstract
Long non-coding RNAs (lncRNAs) have become important regulators of gene expression because they affect a wide range of biological processes, such as cell growth, death, differentiation, and aging. More and more evidence suggests that lncRNAs play a role in maintaining metabolic homeostasis. When certain lncRNAs are out of balance, metabolic disorders like diabetes, obesity, and heart disease get worse. In this review, we talk about what we know about how lncRNAs control metabolism, with a focus on diseases caused by long-term inflammation and the characteristics of the metabolic syndrome. We looked at lncRNAs and their molecular targets in the pathogenesis of signaling pathways. We also talked about how lncRNAs are becoming more and more interesting as diagnostic and therapeutic targets for improving metabolic homeostasis.
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Affiliation(s)
- Mohammad Rashidmayvan
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Reza Sahebi
- Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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39
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MiR-18a-5p Targets Connective Tissue Growth Factor Expression and Inhibits Transforming Growth Factor β2-Induced Trabecular Meshwork Cell Contractility. Genes (Basel) 2022; 13:genes13081500. [PMID: 36011411 PMCID: PMC9408287 DOI: 10.3390/genes13081500] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/16/2022] [Accepted: 08/17/2022] [Indexed: 12/22/2022] Open
Abstract
Increased trabecular meshwork (TM) cell and tissue contractility is a driver of the reduced outflow facility and elevation of intraocular pressure (IOP) associated with primary open-angle glaucoma (POAG). Connective tissue growth factor (CTGF) is an established mediator of TM cell contractility, and its expression is increased in POAG due to transforming growth factor β 2 (TGFβ2) signalling. Inhibiting CTGF upregulation using microRNA (miRNA) mimetics could represent a new treatment option for POAG. A combination of in silico predictive tools and a literature review identified a panel of putative CTGF-targeting miRNAs. Treatment of primary human TM cells with 5 ng/mL TGFβ2 for 24 h identified miR-18a-5p as a consistent responder, being upregulated in cells from five different human donors. Transfection of primary donor TM cells with 20 nM synthetic miR-18a-5p mimic reduced TGFβ2-induced CTGF protein expression, and stable lentiviral-mediated overexpression of this miRNA reduced TGFβ2-induced contraction of collagen gels. Together, these findings identify miR-18a-5p as a mediator of the TGFβ2 response and a candidate therapeutic agent for glaucoma via its ability to inhibit CTGF-associated increased TM contractility.
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40
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Liao B, Dong S, Xu Z, Gao F, Zhang S, Liang R. MiR-19b-3p regulated by BC002059/ABHD10 axis promotes cell apoptosis in myocardial infarction. Biol Direct 2022; 17:20. [PMID: 35978367 PMCID: PMC9386969 DOI: 10.1186/s13062-022-00333-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 07/23/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Recently, microRNAs (miRNAs), have been extensively investigated in diseases. The upregulated expression of miR-19b-3p has been validated in patients with hypertrophic cardiomyopathy. Nonetheless, it regulatory mechanism in myocardial infarction (MI) is still unclear. PURPOSE This research aimed to investigate the role and molecular regulation mechanism of miR-19b-3p in MI. METHODS QRT-PCR and western blot assays measured RNA and protein expression. Cell apoptosis were tested by flow cytometry and TUNEL assays. Cell viability was measured by trypan blue staining method. RIP and luciferase report assays examined gene interaction. The assays were performed under hypoxia condition. RESULTS MiR-19b-3p was highly expressed in myocardial cell line H9C2, primary cardiomyocytes, and tissues from MI mouse model. MiR-19b-3p inhibition suppressed the apoptosis of cardiomyocytes. BC002059 could up-regulate ABHD10 through sequestering miR-19b-3p. BC002059 upregulation was observed to repress cell apoptosis. Rescue experiments demonstrated that miR-19b-3p overexpression abrogated the suppressive impact of BC002059 on the apoptosis of MI cells, and infarct size, area at risk as well as CK-MB and LDH release of MI mouse model tissues, which was further abolished via ABHD10 increment. CONCLUSION MiR-19b-3p regulated by BC002059/ABHD10 axis promotes cell apoptosis in MI, which might provide a novel perspective for MI alleviation research.
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Affiliation(s)
- Bihong Liao
- Department of Cardiology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, 1017 Dongmen North Road, Luohu District, Shenzhen, 518000, Guangdong, China
| | - Shaohong Dong
- Department of Cardiology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, 1017 Dongmen North Road, Luohu District, Shenzhen, 518000, Guangdong, China.
| | - Zhenglei Xu
- Department of Gastroenterology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, 1017 Dongmen North Road, Luohu District, Shenzhen, 518000, Guangdong, China.
| | - Fei Gao
- Department of Cardiology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, 1017 Dongmen North Road, Luohu District, Shenzhen, 518000, Guangdong, China
| | - Suihao Zhang
- Department of Cardiology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, 1017 Dongmen North Road, Luohu District, Shenzhen, 518000, Guangdong, China
| | - Ruijuan Liang
- Department of Cardiology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, 1017 Dongmen North Road, Luohu District, Shenzhen, 518000, Guangdong, China
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41
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Zheng G, He Z, Lu Y, Zhu Q, Jiang Y, Chen D, Lin S, Zhu C, Schwartz R. SRF-derived miR210 and miR30c both repress beating cardiomyocyte formation in the differentiation system of embryoid body. Biochem Biophys Res Commun 2022; 626:58-65. [PMID: 35970045 DOI: 10.1016/j.bbrc.2022.08.016] [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: 07/10/2022] [Revised: 07/16/2022] [Accepted: 08/04/2022] [Indexed: 11/02/2022]
Abstract
Serum response factor (SRF) cooperates with various co-factors to manage the specification of diverse cell lineages during heart development. Many microRNAs mediate the function of SRF in this process. However, how are miR210 and miR30c involved in the decision of cardiac cell fates remains to be explored. In this study, we found that SRF directly controlled the cardiac expression of miR210. Both miR210 and miR30c blocked the formation of beating cardiomyocyte during embryoid body (EB) differentiation, a cellular model widely used for studying cardiogenesis. Both of anticipated microRNA targets and differentially expressed genes in day8 EBs were systematically determined and enriched with gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) and Reactome. Functional enrichments of prediction microRNA targets and down-regulated genes in day8 EBs of miR210 suggested the importance of PI3K-Akt signal and ETS2 in miR210 inhibition of cardiomyocyte differentiation. Similar analyses revealed that miR30c repressed both developmental progress and the adrenergic signaling in cardiomyocytes during the differentiation of EBs. Taken together, SRF directs the expression of miR210 and miR30c, and they repress cardiac development via inhibiting the differentiation of cardiac muscle cell lineage as well as the cell proliferation. Through the regulation of specific microRNAs, the complication of SRF's function in heart development is emphasized.
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Affiliation(s)
- Guoxing Zheng
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China; Department of Biology and Biochemistry, The University of Houston, Houston, TX, USA.
| | - Zhuzhen He
- Shenzhen Amcare Maternity Hospital, Shenzhen, Guangdong, 518052, China
| | - Yingsi Lu
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China
| | - Qingqing Zhu
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China
| | - Yizhou Jiang
- Institute for Advanced Study, Shenzhen University, Shenzhen, Guangdong, 518060, China
| | - Demeng Chen
- Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Shuibin Lin
- Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China
| | - Chengming Zhu
- The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, 518107, China
| | - Robert Schwartz
- Department of Biology and Biochemistry, The University of Houston, Houston, TX, USA.
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42
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New Insights into the Functions of MicroRNAs in Cardiac Fibrosis: From Mechanisms to Therapeutic Strategies. Genes (Basel) 2022; 13:genes13081390. [PMID: 36011301 PMCID: PMC9407613 DOI: 10.3390/genes13081390] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 07/16/2022] [Accepted: 08/03/2022] [Indexed: 02/06/2023] Open
Abstract
Cardiac fibrosis is a significant global health problem associated with almost all types of heart disease. Extensive cardiac fibrosis reduces tissue compliance and contributes to adverse outcomes, such as cardiomyocyte hypertrophy, cardiomyocyte apoptosis, and even heart failure. It is mainly associated with pathological myocardial remodeling, characterized by the excessive deposition of extracellular matrix (ECM) proteins in cardiac parenchymal tissues. In recent years, a growing body of evidence demonstrated that microRNAs (miRNAs) have a crucial role in the pathological development of cardiac fibrosis. More than sixty miRNAs have been associated with the progression of cardiac fibrosis. In this review, we summarized potential miRNAs and miRNAs-related regulatory mechanisms for cardiac fibrosis and discussed the potential clinical application of miRNAs in cardiac fibrosis.
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43
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Targeting Myocardial Fibrosis—A Magic Pill in Cardiovascular Medicine? Pharmaceutics 2022; 14:pharmaceutics14081599. [PMID: 36015225 PMCID: PMC9414721 DOI: 10.3390/pharmaceutics14081599] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 07/27/2022] [Accepted: 07/28/2022] [Indexed: 11/16/2022] Open
Abstract
Fibrosis, characterized by an excessive accumulation of extracellular matrix, has long been seen as an adaptive process that contributes to tissue healing and regeneration. More recently, however, cardiac fibrosis has been shown to be a central element in many cardiovascular diseases (CVDs), contributing to the alteration of cardiac electrical and mechanical functions in a wide range of clinical settings. This paper aims to provide a comprehensive review of cardiac fibrosis, with a focus on the main pathophysiological pathways involved in its onset and progression, its role in various cardiovascular conditions, and on the potential of currently available and emerging therapeutic strategies to counteract the development and/or progression of fibrosis in CVDs. We also emphasize a number of questions that remain to be answered, and we identify hotspots for future research.
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44
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Dong Y, Peng N, Dong L, Tan S, Zhang X. Non-coding RNAs: Important participants in cardiac fibrosis. Front Cardiovasc Med 2022; 9:937995. [PMID: 35966549 PMCID: PMC9365961 DOI: 10.3389/fcvm.2022.937995] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 06/24/2022] [Indexed: 11/24/2022] Open
Abstract
Cardiac remodeling is a pathophysiological process activated by diverse cardiac stress, which impairs cardiac function and leads to adverse clinical outcome. This remodeling partly attributes to cardiac fibrosis, which is a result of differentiation of cardiac fibroblasts to myofibroblasts and the production of excessive extracellular matrix within the myocardium. Non-coding RNAs mainly include microRNAs and long non-coding RNAs. These non-coding RNAs have been proved to have a profound impact on biological behaviors of various cardiac cell types and play a pivotal role in the development of cardiac fibrosis. This review aims to summarize the role of microRNAs and long non-coding RNAs in cardiac fibrosis associated with pressure overload, ischemia, diabetes mellitus, aging, atrial fibrillation and heart transplantation, meanwhile shed light on the diagnostic and therapeutic potential of non-coding RNAs for cardiac fibrosis.
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45
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Li G, Yang J, Zhang D, Wang X, Han J, Guo X. Research Progress of Myocardial Fibrosis and Atrial Fibrillation. Front Cardiovasc Med 2022; 9:889706. [PMID: 35958428 PMCID: PMC9357935 DOI: 10.3389/fcvm.2022.889706] [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: 03/04/2022] [Accepted: 06/10/2022] [Indexed: 12/04/2022] Open
Abstract
With the aging population and the increasing incidence of basic illnesses such as hypertension and diabetes (DM), the incidence of atrial fibrillation (AF) has increased significantly. AF is the most common arrhythmia in clinical practice, which can cause heart failure (HF) and ischemic stroke (IS), increasing disability and mortality. Current studies point out that myocardial fibrosis (MF) is one of the most critical substrates for the occurrence and maintenance of AF. Although myocardial biopsy is the gold standard for evaluating MF, it is rarely used in clinical practice because it is an invasive procedure. In addition, serological indicators and imaging methods have also been used to evaluate MF. Nevertheless, the accuracy of serological markers in evaluating MF is controversial. This review focuses on the pathogenesis of MF, serological evaluation, imaging evaluation, and anti-fibrosis treatment to discuss the existing problems and provide new ideas for MF and AF evaluation and treatment.
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Affiliation(s)
- Guangling Li
- Department of Cardiology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China
| | - Jing Yang
- Department of Pathology, Gansu Provincial Hospital, Lanzhou, China
| | - Demei Zhang
- Department of Cardiology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China
| | - Xiaomei Wang
- Department of Cardiology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China
| | - Jingjing Han
- Department of Cardiology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China
| | - Xueya Guo
- Department of Cardiology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China
- *Correspondence: Xueya Guo,
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Woudenberg T, Kruyt ND, Quax PHA, Nossent AY. Change of Heart: the Epitranscriptome of Small Non-coding RNAs in Heart Failure. Curr Heart Fail Rep 2022; 19:255-266. [PMID: 35876969 PMCID: PMC9534797 DOI: 10.1007/s11897-022-00561-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/05/2022] [Indexed: 12/25/2022]
Abstract
Purpose of Review Small non-coding RNAs regulate gene expression and are highly implicated in heart failure. Recently, an additional level of post-transcriptional regulation has been identified, referred to as the epitranscriptome, which encompasses the body of post-transcriptional modifications that are placed on RNA molecules. In this review, we summarize the current knowledge on the small non-coding RNA epitranscriptome in heart failure. Recent Findings With the rise of new methods to study RNA modifications, epitranscriptome research has begun to take flight. Over the past 3 years, the number of publications on the epitranscriptome in heart failure has significantly increased, and we expect many more highly relevant publications to come out over the next few years. Summary Currently, at least six modifications on small non-coding RNAs have been investigated in heart failure-relevant studies, namely N6-adenosine, N5-cytosine and N7-guanosine methylation, 2’-O-ribose-methylation, adenosine-to-inosine editing, and isomiRs. Their potential role in heart failure is discussed.
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Affiliation(s)
- Tamar Woudenberg
- Department of Surgery, Leiden University Medical Center, D6-P, PO Box 9600, 2300 RC, Leiden, the Netherlands.,Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands
| | - Nyika D Kruyt
- Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands
| | - Paul H A Quax
- Department of Surgery, Leiden University Medical Center, D6-P, PO Box 9600, 2300 RC, Leiden, the Netherlands.,Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands
| | - A Yaël Nossent
- Department of Surgery, Leiden University Medical Center, D6-P, PO Box 9600, 2300 RC, Leiden, the Netherlands. .,Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
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MicroRNAs in Dystrophinopathy. Int J Mol Sci 2022; 23:ijms23147785. [PMID: 35887128 PMCID: PMC9318410 DOI: 10.3390/ijms23147785] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Revised: 07/12/2022] [Accepted: 07/13/2022] [Indexed: 11/17/2022] Open
Abstract
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), which represent the range of dystrophinopathies, account for nearly 80% of muscle dystrophy. DMD and BMD result from the loss of a functional dystrophin protein, and the leading cause of death in these patients is cardiac remodeling and heart failure. The pathogenesis and progression of the more severe form of DMD have been extensively studied and are controlled by many determinants, including microRNAs (miRNAs). The regulatory role of miRNAs in muscle function and the differential miRNA expression in muscular dystrophy indicate the clinical significance of miRNAs. This review discusses the relevant microRNAs as potential biomarkers and therapeutic targets for DMD and DMD cardiomyopathy as examples of dystrophinopathies.
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Xiang K, Akram M, Elbossaty WF, Yang J, Fan C. Exosomes in atrial fibrillation: therapeutic potential and role as clinical biomarkers. Heart Fail Rev 2022; 27:1211-1221. [PMID: 34251579 DOI: 10.1007/s10741-021-10142-5] [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] [Accepted: 07/05/2021] [Indexed: 12/21/2022]
Abstract
Atrial fibrillation (AF), the most common cardiac arrhythmia, is a global epidemic. AF can cause heart failure and myocardial infarction and increase the risk of stroke, disability, and thromboembolic events. AF is becoming increasingly ubiquitous and is associated with increased morbidity and mortality at higher ages, resulting in an increasing threat to human health as well as substantial medical and social costs. Currently, treatment strategies for AF focus on controlling heart rate and rhythm with medications to restore and maintain sinus rhythm, but this approach has limitations. Catheter ablation is not entirely satisfactory and does not address the issues underlying AF. Research exploring the mechanisms causing AF is urgently needed for improved prevention, diagnosis, and treatment of AF. Exosomes are small vesicles (30-150 nm) released by cells that transmit information between cells. MicroRNAs in exosomes play an important role in the pathogenesis of AF and are established as a biomarker for AF. In this review, a summary of the role of exosomes in AF is presented. The role of exosomes and microRNAs in AF occurrence, their therapeutic potential, and their potential role as clinical biomarkers is considered. A better understanding of exosomes has the potential to improve the prognosis of AF patients worldwide, reducing the global medical burden of this disease.
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Affiliation(s)
- Kun Xiang
- Department of Cardiovascular Surgery, the Second Xiangya Hospital, Central South University, Middle Renmin Road 139, Changsha, 410011, China
| | - Muhammad Akram
- Department of Eastern Medicine, Government College University Faisalabad, Faisalabad, Pakistan
| | | | - Jinfu Yang
- Department of Cardiovascular Surgery, the Second Xiangya Hospital, Central South University, Middle Renmin Road 139, Changsha, 410011, China
| | - Chengming Fan
- Department of Cardiovascular Surgery, the Second Xiangya Hospital, Central South University, Middle Renmin Road 139, Changsha, 410011, China.
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Abstract
Diabetes is a metabolic disorder that affects millions of people worldwide. Diabetic heart disease (DHD) comprises coronary artery disease, heart failure, cardiac autonomic neuropathy, peripheral arterial disease, and diabetic cardiomyopathy. The onset and progression of DHD have been attributed to molecular alterations in response to hyperglycemia in diabetes. In this context, microRNAs (miRNAs) have been demonstrated to have a significant role in the development and progression of DHD. In addition to their effects on the host cells, miRNAs can be released into circulation after encapsulation within the exosomes. Exosomes are extracellular nanovesicles ranging from 30 to 180 nm in diameter secreted by all cell types. They carry diverse cargos that are altered in response to various conditions in their parent cells. Exosomal miRNAs have been extensively studied in recent years due to their role and therapeutic potential in DHD. This review will first provide an overview of exosomes, their biogenesis and function, followed by the role of exosomes in cardiovascular disease and then focuses on the known role of exosomes and associated miRNAs in DHD.
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Affiliation(s)
- Dhananjie Chandrasekera
- Department of Physiology, School of Biomedical Sciences, HeartOtago, University of Otago, 270, Great King Street, Dunedin, New Zealand.
| | - Rajesh Katare
- Department of Physiology, School of Biomedical Sciences, HeartOtago, University of Otago, 270, Great King Street, Dunedin, New Zealand.
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Hu CK, Cai RP, He L, He SR, Liao JY, Su Q. A Nomogram model for predicting the occurrence of no-reflow phenomenon after percutaneous coronary intervention using the lncRNA TUG1/miR-30e/ NPPB biomarkers. J Thorac Dis 2022; 14:2158-2168. [PMID: 35813727 PMCID: PMC9264104 DOI: 10.21037/jtd-22-481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Accepted: 06/20/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Studies have shown that percutaneous coronary intervention (PCI) is considered as the essential therapeutic strategy for the patients with ST-segment elevation myocardial infarction (STEMI). However; no-reflow could still occur in a few patients after PCI. Studies have reported that biomarkers related to no-reflow pathogenetic components could play a prognostic role in the prediction phenomenon. Hence, this study explored the establishment of nomogram model for predicting the occurrence of no-reflow phenomenon after PCI using the lncRNA TUG1/miR-30e/NPPB biomarkers in patients with STEMI after PCI. METHODS In this observational study, a total of 76 STEMI patients who underwent emergency PCI between January 2018 and December 2021were included. The patients after PCI, were divided into reflow (n=44) and no-reflow groups (n=32). The demographic, environmental and clinical risk factors were assessed and analysed between the groups. Quantitative RT-PCR was used to detect TUG1, miR-30e, and NPPB messenger RNA (mRNA) expression levels in the plasma of patients after PCI. Bioinformatic methods were used to predict the interaction of the plasma TUG1/miR-30e/NPPB axis. The risk factors in the no-reflow group were screened using a logistic-regression analysis, and a nomogram prediction model was constructed and validated. Subsequently, a gene set enrichment analysis revealed the function of lncRNA TUG1. RESULTS Plasma lncRNA TUG1 and NPPB were more highly expressed and miR-30e was more lowly expressed in the no-reflow group than the normal-reflow group (P<0.001). A negative correlation was observed between lncRNA TUG1 and miR-30e, and between miR-30e and NPPB. However, a positive correlation was observed between lncRNA TUG1 and NPPB mRNA. The bioinformatics analysis predicted multiple binding sites on the lncRNA TUG1 and miR-30e. LncRNA TUG1 [odds ratio (OR): 0.163, 95% confidence interval (CI): 0.021-0.944] and hs-CRP (OR: 2.151, 95% CI: 1.536-3.974) found to be as independent predictors. The C-index of this prediction model was 0.982 (95% CI: 0.956-1.000). CONCLUSIONS TUG1 could function as an effective biomarker for no-reflow among patients with STEMI after PCT and the proposed nomogram may provide information for individualized treatment in patients with STEMI.
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Affiliation(s)
- Chen-Kai Hu
- Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Ru-Ping Cai
- Department of Cardiology, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Lei He
- Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Shi-Rong He
- Department of Cardiology, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Jun-Yu Liao
- Department of Cardiology, Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Qiang Su
- Department of Cardiology, Affiliated Hospital of Guilin Medical University, Guilin, China
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