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Ma X, Chu H, Sun Y, Cheng Y, Zhang D, Yang L, Wang Z, Liu X, Zhou Y. Prognostic significance of stress hyperglycemia ratio in patients with type 2 diabetes mellitus and acute coronary syndromes. Thromb J 2025; 23:47. [PMID: 40355885 PMCID: PMC12067665 DOI: 10.1186/s12959-025-00729-5] [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: 11/01/2024] [Accepted: 04/29/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Prognostic significance of stress hyperglycemia ratio (SHR) has not been well studied in patients with type 2 diabetes mellitus (T2DM) and acute coronary syndromes (ACS). METHODS We prospectively measured admission fasting blood glucose (AFBG) and glycated hemoglobin A1c (HbA1c), and retrospectively calculated the stress hyperglycemia ratio (SHR, = AFBG/[1.59 × HbA1c (%) - 2.59]) in 791 patients with T2DM and ACS undergoing percutaneous coronary intervention (PCI). The primary endpoint was defined as major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause mortality, non-fatal stroke, non-fatal myocardial infarction, and unplanned repeat coronary revascularization. RESULTS The mean age of the study population was 61 ± 10 years, and 72.8% were male. Over a median follow-up of 927 days, 194 patients developed at least one primary endpoint event. The follow-up incidence of MACCE increased in parallel with SHR tertiles (15.6%, 21.9%, and 36.1%, respectively; P for trend < 0.001). The Cox proportional hazards regression analysis adjusted for multiple confounding factors showed hazard ratios for MACCE of 1.525 (95% CI: 1.009-2.305; P = 0.045) for the middle tertile and 2.525 (95% CI: 1.729-3.687; P < 0.001) for the highest tertile of SHR, with the lowest tertile as the reference. The addition of SHR to the baseline reference prediction model improved model predictive performance markedly (C-statistic: increased from 0.704 to 0.721; cNRI: 0.176 [95% CI: 0.063-0.282], P = 0.002; IDI: 0.030 [95% CI: 0.009-0.063], P = 0.002). CONCLUSION SHR was independently and significantly associated with adverse cardiovascular outcomes in T2DM and ACS patients who underwent PCI, and had an incremental effect on the predictive ability of the baseline reference prediction model.
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Affiliation(s)
- Xiaoteng Ma
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Huijun Chu
- Department of Anesthesia, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yan Sun
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Yujing Cheng
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Dai Zhang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Lixia Yang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Zhijian Wang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Xiaoli Liu
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Yujie Zhou
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
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Sullivan AE, Courvan MCS, Aday AW, Wasserman DH, Niswender KD, Shardelow EM, Wells EK, Wells QS, Freiberg MS, Beckman JA. The Role of Serum Free Fatty Acids in Endothelium-Dependent Microvascular Function. Endocrinol Diabetes Metab 2025; 8:e70031. [PMID: 39888728 PMCID: PMC11784902 DOI: 10.1002/edm2.70031] [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: 10/09/2024] [Revised: 12/28/2024] [Accepted: 01/11/2025] [Indexed: 02/02/2025] Open
Abstract
BACKGROUND Elevated serum free fatty acid (FFA) concentration is associated with insulin resistance and is a hallmark of metabolic syndrome. A pathological feature of insulin resistance is impaired endothelial function. OBJECTIVE To investigate the effect of FFA reduction with either acipimox, a nicotinic acid derivative that impairs lipolysis, or salsalate, a salicylate that reduces basal and inflammation-induced lipolysis, on insulin-mediated endothelium-dependent vasodilation. METHODS This was a post hoc, combined analysis of two randomised, double-blind, placebo-controlled crossover trials. Sixteen subjects were recruited (6 with metabolic syndrome and 10 controls) and randomised to acipimox 250 mg orally every 6 h for 7 days or placebo. Nineteen subjects were recruited (13 with metabolic syndrome and 6 controls) and randomised to receive salsalate 4.5 g/day for 4 weeks or placebo. The primary outcome was the association between FFA concentration and insulin-mediated vasodilation, measured by venous-occlusion strain-gauge plethysmography at baseline and following FFA modulation with the study drugs. RESULTS At baseline, FFA concentration (R = -0.35, p = 0.043) and insulin sensitivity (HOMA-IR: R = -0.42, p = 0.016, Adipo-IR: R = -0.39, p = 0.025) predicted insulin-mediated vasodilation. FFA levels were significantly reduced after drug pretreatment (0.604 vs. 0.491 mmol/L, p = 0.036) while insulin levels, insulin sensitivity and inflammatory markers were unchanged. Despite a reduction in circulating FFA with drug therapy, neither insulin-stimulated vasodilation nor insulin sensitivity improved. CONCLUSIONS Short-term reduction of FFA concentration does not improve insulin-stimulated vasodilation in patients with metabolic syndrome. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00759291 and NCT00760019 (formerly NCT00762827).
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Affiliation(s)
- Alexander E. Sullivan
- Division of Cardiovascular Medicine, Department of MedicineVanderbilt University Medical CenterNashvilleTennesseeUSA
| | | | - Aaron W. Aday
- Division of Cardiovascular Medicine, Department of MedicineVanderbilt University Medical CenterNashvilleTennesseeUSA
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Division of Cardiovascular MedicineVanderbilt University Medical CenterNashvilleTennesseeUSA
| | - David H. Wasserman
- Department of Molecular Physiology and BiophysicsVanderbilt University School of MedicineNashvilleTennesseeUSA
| | - Kevin D. Niswender
- Department of MedicineVanderbilt University Medical CenterNashvilleTennesseeUSA
- Department of Veteran AffairsTennessee Valley Healthcare SystemNashvilleTennesseeUSA
| | - Emily M. Shardelow
- Vanderbilt University Medical CenterProgram for Metabolic Bone DisordersNashvilleTennesseeUSA
| | - Emily K. Wells
- Division of Cardiovascular Medicine, Department of MedicineVanderbilt University Medical CenterNashvilleTennesseeUSA
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Division of Cardiovascular MedicineVanderbilt University Medical CenterNashvilleTennesseeUSA
| | - Quinn S. Wells
- Division of Cardiovascular Medicine, Department of MedicineVanderbilt University Medical CenterNashvilleTennesseeUSA
- Vanderbilt Translational and Clinical Cardiovascular Research Center, Division of Cardiovascular MedicineVanderbilt University Medical CenterNashvilleTennesseeUSA
| | - Matthew S. Freiberg
- Division of Cardiovascular Medicine, Department of MedicineVanderbilt University Medical CenterNashvilleTennesseeUSA
- Geriatric Research Education and Clinical Centers (GRECC)Veterans Affairs Tennessee Valley Healthcare SystemNashvilleTennesseeUSA
| | - Joshua A. Beckman
- Division of Vascular Medicine, Department of MedicineUniversity of Texas SouthwesternDallasTexasUSA
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Mallik S, Paria B, Firdous SM, Ghazzawy HS, Alqahtani NK, He Y, Li X, Gouda MM. The positive implication of natural antioxidants on oxidative stress-mediated diabetes mellitus complications. J Genet Eng Biotechnol 2024; 22:100424. [PMID: 39674630 PMCID: PMC11416289 DOI: 10.1016/j.jgeb.2024.100424] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 08/22/2024] [Accepted: 08/29/2024] [Indexed: 12/16/2024]
Abstract
The complementary intervention to modulate diabetes mellitus (DM) metabolism has recently brought the global attention, since DM has become among the global burden diseases. Where, several related pathways elevate the production of superoxide in consequences. For example, the flux of glycation-derived end products (AGEs) could lead to the deactivation of insulin signaling pathways. In that context, many vitamins and phytochemicals in natural sources have high antioxidant impacts that reduce oxidative stress and cell damages. These chemicals could be applied as bioactive antidiabetic agents. Their mode of actions could be from regulating the intracellular reactive oxygen species (ROS) which cause several pro-inflammatory pathways related to the oxidative stress (OS) and DM. Besides, they have a great potential to control the epigenetic mutations and hyperglycemia and help in back the blood glucose to the normal level. Therefore, the current review addresses the important role of natural functional antioxidants in DM management and its association with its OS complications.
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Affiliation(s)
- Shouvik Mallik
- Department of Pharmacology, Calcutta Institute of Pharmaceutical Technology & AHS, Uluberia, Howrah, West Bengal, India
| | - Bijoy Paria
- Department of Pharmacology, Calcutta Institute of Pharmaceutical Technology & AHS, Uluberia, Howrah, West Bengal, India
| | - Sayed Mohammad Firdous
- Department of Pharmacology, Calcutta Institute of Pharmaceutical Technology & AHS, Uluberia, Howrah, West Bengal, India.
| | - Hesham S Ghazzawy
- Date Palm Research Center of Excellence, King Faisal University, Al Ahsa, Saudi Arabia; Central Laboratory for Date Palm Research and Development, Agriculture Research Center, Giza 12511, Egypt.
| | - Nashi K Alqahtani
- Date Palm Research Center of Excellence, King Faisal University, Al Ahsa, Saudi Arabia
| | - Yong He
- College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China
| | - Xiaoli Li
- College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China.
| | - Mostafa M Gouda
- College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, China; Department of Nutrition & Food Science, National Research Centre, Dokki, Giza 12622, Egypt.
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Huang K, Yin S, Xiao Y, Wang J, Cui J, Wang J, Bai Y. Sexual dysfunction in patients with diabetes: association between remnant cholesterol and erectile dysfunction. Lipids Health Dis 2024; 23:55. [PMID: 38388371 PMCID: PMC10882869 DOI: 10.1186/s12944-024-02046-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Accepted: 02/13/2024] [Indexed: 02/24/2024] Open
Abstract
BACKGROUND Erectile dysfunction (ED) is closely associated with dyslipidemia; however, it is yet unknown how ED and remnant cholesterol (RC) are related. As such, this research sought to explore the correlation between RC and ED among individuals with diagnosed with diabetes. METHODS This cross-sectional study used information from 215 males from National Health and Nutrition Examination Survey (NHANES) from 2001 to 2004. RC was calculated as follows: the values of high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) were subtracted from the total cholesterol (TC) value, while ED diagnoses were based on self-reports. Weighted logistic regression analyses using both univariate and multivariate approaches were conducted to assess the correlation between RC and ED. RESULTS After comprehensive adjustment, multivariable logistic regression models revealed a strong correlation between RC and ED in subjects with diabetes (with an odds ratio (OR) of 7.49 and a 95% confidence interval (CI) of 1.98-28.37; P = 0.004). On categorizing RC into 3 grades (T1-T3), the OR corresponding to higher RC grade increased. Despite the results not reaching statistical significance upon categorization, a consistent and statistically significant trend (P for trend < 0.05) was observed. CONCLUSION This study indicated a correlation between increased RC levels and a higher prevalence of ED in diabetic males. RC may serve as a promising predictor of ED in individuals with diabetes. However, additional studies are required to confirm these findings.
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Affiliation(s)
- Ke Huang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan, People's Republic of China
| | - Shan Yin
- Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Yunfei Xiao
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan, People's Republic of China
| | - Jiahao Wang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan, People's Republic of China
| | - Jianwei Cui
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan, People's Republic of China
| | - Jia Wang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan, People's Republic of China.
| | - Yunjin Bai
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, 610041, Sichuan, People's Republic of China.
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Di Pietrantonio N, Cappellacci I, Mandatori D, Baldassarre MPA, Pandolfi A, Pipino C. Role of Epigenetics and Metabolomics in Predicting Endothelial Dysfunction in Type 2 Diabetes. Adv Biol (Weinh) 2023; 7:e2300172. [PMID: 37616517 DOI: 10.1002/adbi.202300172] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 06/15/2023] [Indexed: 08/26/2023]
Abstract
Type 2 diabetes (T2D) is a worldwide health problem and cardiovascular disease (CVD) is a leading cause of morbidity and mortality in T2D patients, making the prevention of CVD onset a major priority. It is therefore crucial to optimize diagnosis and treatment to reduce this burden. Endothelial dysfunction is one of the most important prognostic factors for CVD progression, thus novel approaches to identify the early phase of endothelial dysfunction may lead to specific preventive measures to reduce the occurrence of CVD. Nowadays, multiomics approaches have provided unprecedented opportunities to stratify T2D patients into endotypes, improve therapeutic treatment and outcome and amend the survival prediction. Among omics strategies, epigenetics and metabolomics are gaining increasing interest. Recently, a dynamic correlation between metabolic pathways and gene expression through chromatin remodeling, such as DNA methylation, has emerged, indicating new perspectives on the regulatory networks impacting cellular processes. Thus, a better understanding of epigenetic-metabolite relationships can provide insight into the physiological processes altered early in the endothelium that ultimately head to disease development. Here, recent studies on epigenetics and metabolomics related to CVD prevention potentially useful to identify disease biomarkers, as well as new therapies hopefully targeting the early phase of endothelial dysfunction are highlighted.
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Affiliation(s)
- Nadia Di Pietrantonio
- Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, 66100, Italy
- Center for Advanced Studies and Technology-CAST, "G. d'Annunzio" University of Chieti-Pescara, Chieti, 66100, Italy
| | - Ilaria Cappellacci
- Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, 66100, Italy
- Center for Advanced Studies and Technology-CAST, "G. d'Annunzio" University of Chieti-Pescara, Chieti, 66100, Italy
| | - Domitilla Mandatori
- Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, 66100, Italy
- Center for Advanced Studies and Technology-CAST, "G. d'Annunzio" University of Chieti-Pescara, Chieti, 66100, Italy
| | - Maria Pompea Antonia Baldassarre
- Center for Advanced Studies and Technology-CAST, "G. d'Annunzio" University of Chieti-Pescara, Chieti, 66100, Italy
- Department of Medicine and Aging Sciences, "G. d'Annunzio" University Chieti-Pescara, Chieti, 66100, Italy
| | - Assunta Pandolfi
- Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, 66100, Italy
- Center for Advanced Studies and Technology-CAST, "G. d'Annunzio" University of Chieti-Pescara, Chieti, 66100, Italy
| | - Caterina Pipino
- Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, 66100, Italy
- Center for Advanced Studies and Technology-CAST, "G. d'Annunzio" University of Chieti-Pescara, Chieti, 66100, Italy
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Mashayekhi M, Beckman JA, Nian H, Garner EM, Mayfield D, Devin JK, Koethe JR, Brown JD, Cahill KN, Yu C, Silver H, Niswender K, Luther JM, Brown NJ. Comparative effects of weight loss and incretin-based therapies on vascular endothelial function, fibrinolysis and inflammation in individuals with obesity and prediabetes: A randomized controlled trial. Diabetes Obes Metab 2023; 25:570-580. [PMID: 36306151 PMCID: PMC10306232 DOI: 10.1111/dom.14903] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 10/10/2022] [Accepted: 10/24/2022] [Indexed: 02/02/2023]
Abstract
AIM To test the hypothesis that glucagon-like peptide-1 receptor (GLP-1R) agonists have beneficial effects on vascular endothelial function, fibrinolysis and inflammation through weight loss-independent mechanisms. MATERIALS AND METHODS Individuals with obesity and prediabetes were randomized to 14 weeks of the GLP-1R agonist liraglutide, hypocaloric diet or the dipeptidyl peptidase-4 inhibitor sitagliptin in a 2:1:1 ratio. Treatment with drug was double blind and placebo-controlled. Measurements were made at baseline, after 2 weeks prior to significant weight loss and after 14 weeks. The primary outcomes were measures of endothelial function: flow-mediated vasodilation (FMD), plasminogen activator inhibitor-1 (PAI-1) and urine albumin-to-creatinine ratio (UACR). RESULTS Eighty-eight individuals were studied (liraglutide N = 44, diet N = 22, sitagliptin N = 22). Liraglutide and diet reduced weight, insulin resistance and PAI-1, while sitagliptin did not. There was no significant effect of any treatment on endothelial vasodilator function measured by FMD. Post hoc subgroup analyses in individuals with baseline FMD below the median, indicative of greater endothelial dysfunction, showed an improvement in FMD by all three treatments. GLP-1R antagonism with exendin (9-39) increased fasting blood glucose but did not change FMD or PAI-1. There was no effect of treatment on UACR. Finally, liraglutide, but not sitagliptin or diet, reduced the chemokine monocyte chemoattractant protein-1 (MCP-1). CONCLUSION Liraglutide and diet reduce weight, insulin resistance and PAI-1. Liraglutide, sitagliptin and diet do not change FMD in obese individuals with prediabetes with normal endothelial function. Liraglutide alone lowers the pro-inflammatory and pro-atherosclerotic chemokine MCP-1, indicating that this beneficial effect is independent of weight loss.
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Affiliation(s)
- Mona Mashayekhi
- Vanderbilt University Medical Center, Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Nashville, TN
| | - Joshua A. Beckman
- Vanderbilt University Medical Center, Department of Medicine, Division of Cardiovascular Medicine, Nashville, TN
| | - Hui Nian
- Vanderbilt University Medical Center, Department of Biostatistics, Nashville, TN
| | - Erica M. Garner
- Vanderbilt University Medical Center, Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Nashville, TN
| | - Dustin Mayfield
- Vanderbilt University Medical Center, Department of Medicine, Division of Clinical Pharmacology, Nashville, TN
| | - Jessica K. Devin
- UCHealth Endocrinology, Yampa Valley Medical Center, Steamboat Springs, CO
| | - John R. Koethe
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN
- Vanderbilt University Medical Center, Department of Medicine, Division of Infectious Diseases, Nashville, TN
| | - Jonathan D. Brown
- Vanderbilt University Medical Center, Department of Medicine, Division of Cardiovascular Medicine, Nashville, TN
| | - Katherine N. Cahill
- Vanderbilt University Medical Center, Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Nashville, TN
| | - Chang Yu
- NYU Grossman School of Medicine, Department of Population Health, New York, NY
| | - Heidi Silver
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN
- Vanderbilt University Medical Center, Department of Medicine, Division of Gastroenterology, Nashville, TN
| | - Kevin Niswender
- Vanderbilt University Medical Center, Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Nashville, TN
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN
| | - James M. Luther
- Vanderbilt University Medical Center, Department of Medicine, Division of Clinical Pharmacology, Nashville, TN
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Mason SA, Parker L, van der Pligt P, Wadley GD. Vitamin C supplementation for diabetes management: A comprehensive narrative review. Free Radic Biol Med 2023; 194:255-283. [PMID: 36526243 DOI: 10.1016/j.freeradbiomed.2022.12.003] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 12/01/2022] [Accepted: 12/05/2022] [Indexed: 12/15/2022]
Abstract
Growing evidence suggests that vitamin C supplementation may be an effective adjunct therapy in the management of people with diabetes. This paper critically reviews the current evidence on effects of vitamin C supplementation and its potential mechanisms in diabetes management. Evidence from meta-analyses of randomized controlled trials (RCTs) show favourable effects of vitamin C on glycaemic control and blood pressure that may be clinically meaningful, and mixed effects on blood lipids and endothelial function. However, evidence is mostly of low evidence certainty. Emerging evidence is promising for effects of vitamin C supplementation on some diabetes complications, particularly diabetic foot ulcers. However, there is a notable lack of robust and well-designed studies exploring effects of vitamin C as a single compound supplement on diabetes prevention and patient-important outcomes (i.e. prevention and amelioration of diabetes complications). RCTs are also required to investigate potential preventative or ameliorative effects of vitamin C on gestational diabetes outcomes. Oral vitamin C doses of 500-1000 mg per day are potentially effective, safe, and affordable for many individuals with diabetes. However, personalisation of supplementation regimens that consider factors such as vitamin C status, disease status, current glycaemic control, vitamin C intake, redox status, and genotype is important to optimize vitamin C's therapeutic effects safely. Finally, given a high prevalence of vitamin C deficiency in patients with complications, it is recommended that plasma vitamin C concentration be measured and monitored in the clinic setting.
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Affiliation(s)
- Shaun A Mason
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia.
| | - Lewan Parker
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia
| | - Paige van der Pligt
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia; Department of Nutrition and Dietetics, Western Health, Footscray, Australia
| | - Glenn D Wadley
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia
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Armenia A, Wahyuni FS, Almahdy A, Abdillah R, Aquista PG, Putri DP, Zikra M. Blood pressure and blood sugar-lowering effects of purified gambir on diabetic hypertensive Wistar Kyoto rats. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2022; 19:627-636. [PMID: 35446514 DOI: 10.1515/jcim-2022-0054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Accepted: 04/05/2022] [Indexed: 11/15/2022]
Abstract
OBJECTIVES Antioxidants protect people from diabetes and its cardiovascular complication. Purified gambir (Uncaria gambir Roxb.) is a potential medicinal plant for treating this condition based on the antioxidant activity of its catechin compound. This study tries to reveal the potential activity of purified gambir as a blood pressure-lowering drug while lowering blood glucose in diabetic hypertensive rats induced by oral NaCl-Prednisone and Alloxan. METHODS Rats were induced by oral NaCl 0.8% and Prednisone 5 mg/kg BW for 14 days to obtain hypertensive condition. Alloxan 125 mg/kg BW was given intra peritoneal injection on the 8th day to obtain diabetic hypertensive condition. The animal was divided into five groups, normal control group treated with vehicle, treatment groups were treated with purified gambir at dose of 2.5; 5 and 10 mg/kg BW respectively, while the positive control group were treated with a combination of captopril-glibenclamide at dose of 2.25 and 0.45 mg/kg BW. All animals were treated orally for 14 days. Fasting blood glucose and cardiovascular parameters (SBP, DBP, MAP, HR, BF and BV) were measured on days 1, 3, 7, and 14. NO level were measured on day 0 and day 14. Data were analyzed using two-way ANOVA followed by Duncan Multiple Range Test. RESULTS The purified gambir has blood pressure and blood sugar-lowering activity (p<0.05). The NO levels of the treatment group also increased significantly (p<0.05). CONCLUSIONS This study indicated that purified gambir could be an alternative medicine to manage blood glucose and blood pressure in the diabetic hypertensive model.
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Affiliation(s)
- Armenia Armenia
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Andalas, Padang, Indonesia
| | - Fatma Sri Wahyuni
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Andalas, Padang, Indonesia
| | - Almahdy Almahdy
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Andalas, Padang, Indonesia
| | - Rahmad Abdillah
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Andalas, Padang, Indonesia
| | - Popy Genca Aquista
- Undergraduate Pharmacy Study Programme, Faculty of Pharmacy, Universitas Andalas, Padang, Indonesia
| | - Diana Puspita Putri
- Undergraduate Pharmacy Study Programme, Faculty of Pharmacy, Universitas Andalas, Padang, Indonesia
| | - Murhamah Zikra
- Undergraduate Pharmacy Study Programme, Faculty of Pharmacy, Universitas Andalas, Padang, Indonesia
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D'Ambrosi F, Rossi G, Di Maso M, Marino C, Soldavini CM, Caneschi A, Cetera GE, Erra R, Ferrazzi E. Altered Doppler velocimetry of fetal middle cerebral artery in singleton pregnancies complicated by mild well-controlled gestational diabetes. Fetal Diagn Ther 2022; 49:77-84. [PMID: 35104818 DOI: 10.1159/000522203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 01/24/2022] [Indexed: 11/19/2022]
Abstract
Introduction The aim the present study is to evaluate fetal umbilical artery (UA) and middle cerebral artery (MCA) blood flow in patients with gestational diabetes (GD), in order to determine whether minimal anomalies of glucose metabolism may influence fetal placental function. Methods UA and MCA flow were prospectively measured by transabdominal ultrasound in singleton pregnancies between 34 and 37 weeks of gestation. Results The study included 35 women with GD and 217 non-diabetic patients. Middle cerebral pusatility index (PI) was significantly higher in the GD group (mean MCA - PI =1.82±0.27 vs 1.71 ±0.26; p< 0.02). Likewise, MCA peak systolic velocity (MCA-PSV) was higher in the GD group compared to the non-GD group, though the difference was not significant (mean of MCA-PSV =47.14 ±8.45 vs 47.09 ± 11.21; p = 0.98). UA-PI resulted higher in the non-GD group without significant differences (mean of UA-PI =0.88 ±0.14 vs 0.86 ± 0.15; p = 0.32) Conclusions Our study shows that even in cases of minimal metabolic derangements, GD is characterised by a significant variation in fetal Doppler velocimetry, particularly in the brain.
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Affiliation(s)
- Francesco D'Ambrosi
- Department of Woman, Child and Neonate, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Gabriele Rossi
- Department of Woman, Child and Neonate, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Matteo Di Maso
- Department of Clinical Sciences and Community Health, Branch of Medical Statistics, Biometry and Epidemiology "G.A. Maccacaro," Università degli Studi di Milano, Milan, Italy
| | - Cecilia Marino
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
| | - Chiara M Soldavini
- Department of Woman, Child and Neonate, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Agnese Caneschi
- Department of Woman, Child and Neonate, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giulia E Cetera
- Department of Woman, Child and Neonate, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Roberta Erra
- Department of Woman, Child and Neonate, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Enrico Ferrazzi
- Department of Woman, Child and Neonate, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
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10
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Horton WB, Jahn LA, Hartline LM, Aylor KW, Patrie JT, Barrett EJ. Acute hyperglycaemia enhances both vascular endothelial function and cardiac and skeletal muscle microvascular function in healthy humans. J Physiol 2022; 600:949-962. [PMID: 33481251 PMCID: PMC8582001 DOI: 10.1113/jp281286] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 01/15/2021] [Indexed: 12/30/2022] Open
Abstract
KEY POINTS Multiple clinical studies report that acute hyperglycaemia (induced by mixed meal or oral glucose) decreases arterial vascular function in healthy humans. Feeding, however, impacts autonomic output, blood pressure, and insulin and incretin secretion, which may themselves alter vascular function. No prior studies have examined the effect of acute hyperglycaemia on both macro- and microvascular function while controlling plasma insulin concentrations. Macrovascular and microvascular functional responses to euglycaemia and hyperglycaemia were compared. Octreotide was infused throughout both protocols to prevent endogenous insulin release. Acute hyperglycaemia (induced by intravenous glucose) enhanced brachial artery flow-mediated dilatation, increased skeletal muscle microvascular blood volume and flow, and expanded cardiac muscle microvascular blood volume. Compared to other published findings, the results suggest that vascular responses to acute hyperglycaemia differ based on the study population (i.e. normal weight vs. overweight/obese) and/or glucose delivery method (i.e. intravenous vs. oral glucose). ABSTRACT High glucose concentrations acutely provoke endothelial cell oxidative stress and are suggested to trigger diabetes-related macro- and microvascular injury in humans. Multiple clinical studies report that acute hyperglycaemia (induced by mixed meal or oral glucose) decreases arterial vascular function in healthy humans. Feeding, however, impacts autonomic output, blood pressure, and insulin and incretin secretion, which may each independently alter vascular function and obscure the effect of acute hyperglycaemia per se. Surprisingly, no studies have examined the acute effects of intravenous glucose-induced hyperglycaemia on both macro- and microvascular function while controlling plasma insulin concentrations. In this randomized study of healthy young adults, we compared macrovascular (i.e. brachial artery flow-mediated dilatation, carotid-femoral pulse wave velocity and post-ischaemic brachial artery flow velocity) and microvascular (heart and skeletal muscle perfusion by contrast-enhanced ultrasound) functional responses to euglycaemia and hyperglycaemia. Octreotide was infused throughout both protocols to prevent endogenous insulin release. Acute intravenous glucose-induced hyperglycaemia enhanced brachial artery flow-mediated dilatation (P = 0.004), increased skeletal muscle microvascular blood volume and flow (P = 0.001), and expanded cardiac muscle microvascular blood volume (P = 0.014). No measure of vascular function changed during octreotide-maintained euglycaemia. Our findings suggest that unlike meal-provoked acute hyperglycaemia, 4 h of intravenous glucose-induced hyperglycaemia enhances brachial artery flow-mediated dilatation, provokes cardiac and skeletal muscle microvascular function, and does not impair aortic stiffness. Previous findings of acute large artery vascular dysfunction during oral glucose or mixed meal ingestion may be due to differences in study populations and meal-induced humoral or neural factors beyond hyperglycaemia per se. (ClinicalTrials.gov number NCT03520569.).
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Affiliation(s)
- William B Horton
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Linda A Jahn
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Lee M Hartline
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Kevin W Aylor
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - James T Patrie
- Division of Biostatistics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Eugene J Barrett
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
- Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, USA
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11
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Yuan C, Jian Z, Gao X, Jin X, Wang M, Xiang L, Li H, Wang K. Type 2 diabetes mellitus increases risk of erectile dysfunction independent of obesity and dyslipidemia: A Mendelian randomization study. Andrology 2021; 10:518-524. [PMID: 34842357 DOI: 10.1111/andr.13132] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 09/20/2021] [Accepted: 11/21/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND The causal effects of individual risk factors of metabolic syndrome on erectile dysfunction (ED) are still unclear. OBJECTIVES To evaluate the causal effect of risk factors of metabolic syndrome on ED through Mendelian randomization (MR). MATERIALS AND METHODS Data for risk factors were obtained from multiple databases with 173,082-757,601 individuals, and that for ED were collected from a genome-wide association study including 223,805 Europeans. We performed univariate MR analysis using inverse-variance weighted, MR-Egger, weighted-median, weighted mode methods and multivariable MR analysis to evaluate the total and direct causal effects. RESULTS The univariable MR supported that type 2 diabetes mellitus (odds ratios [OR] = 1.14, 95% confidence intervals [CI]: 1.08-1.21, p < 0.001) and body mass index (BMI) (OR = 1.27, 95% CI: 1.12-1.44, p < 0.001) were associated with ED. After excluding the SNPs associated with BMI and other risk factors, the results of multivariable MR for T2D (OR = 1.15, 95% CI: 1.05-1.25, p = 0.001) remained consistent. However, the results of multivariable MR provided limited evidence for the causality between BMI and ED (OR = 1.06, 95% CI: 0.88-1.29, p = 0.532). For systolic blood pressure and lipid components (low-density lipoprotein, high-density lipoprotein and triglycerides), both univariable and multivariable MR failed to offer sufficient evidence to confirm their causal effect on ED. CONCLUSION T2D showed a direct causal effect on ED independent of obesity and dyslipidemia.
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Affiliation(s)
- Chi Yuan
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Zhongyu Jian
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, P.R. China.,West China Biomedical Big Data Center, Sichuan University, Chengdu, P.R. China
| | - Xiaoshuai Gao
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Xi Jin
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Menghua Wang
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Liyuan Xiang
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Hong Li
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Kunjie Wang
- Department of Urology, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, P.R. China
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12
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The Acute Effect of Magnesium Supplementation on Endothelial Function: A Randomized Cross-Over Pilot Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18105303. [PMID: 34067524 PMCID: PMC8156719 DOI: 10.3390/ijerph18105303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 04/29/2021] [Accepted: 05/14/2021] [Indexed: 11/17/2022]
Abstract
Magnesium (Mg) deficiency might be a catalyst in the process of endothelial dysfunction, an early event in the pathogenesis of atherosclerosis. The aim of this study was to determine the acute effect of an oral Mg supplement as compared to control on endothelial function assessed by flow-mediated dilatation (FMD). Nineteen participants (39 years, body mass index (BMI) 22.9 kg/m2) completed this randomized cross-over study. Blood pressure (BP) and FMD were measured and blood samples were taken before participants drank 200 mL water, with or without an over the counter Mg supplement (450 mg and 300 mg for men and women). Measurements were repeated at 60 and 120 min. There was a statistically significant two-way interaction between treatment and time on serum Mg (p = 0.037). A difference of −0.085 mm in FMD was observed 60-min post drink in the control group, as compared to baseline FMD, and no difference was observed in the supplement group as compared to baseline. Despite the non-significant interaction between treatment and time on FMD, once adjusted for baseline, the difference seen in the control group and the lack of change in the supplement group at 60 min post-drink suggests that Mg might attenuate the reduction in FMD post-prandially.
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13
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Horton WB, Jahn LA, Hartline LM, Aylor KW, Patrie JT, Barrett EJ. Insulin increases central aortic stiffness in response to hyperglycemia in healthy humans: A randomized four-arm study. Diab Vasc Dis Res 2021; 18:14791641211011009. [PMID: 33908285 PMCID: PMC8481749 DOI: 10.1177/14791641211011009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
INTRODUCTION Increasing arterial stiffness is a feature of vascular aging that is accelerated by conditions that enhance cardiovascular risk, including diabetes mellitus. Multiple studies demonstrate divergence of carotid-femoral pulse wave velocity and augmentation index in persons with diabetes mellitus, though mechanisms responsible for this are unclear. MATERIALS AND METHODS We tested the effect of acutely and independently increasing plasma glucose, plasma insulin, or both on hemodynamic function and markers of arterial stiffness (including carotid-femoral pulse wave velocity, augmentation index, forward and backward wave reflection amplitude, and wave reflection magnitude) in a four-arm, randomized study of healthy young adults. RESULTS Carotid-femoral pulse wave velocity increased only during hyperglycemic-hyperinsulinemia (+0.36 m/s; p = 0.032), while other markers of arterial stiffness did not change (all p > 0.05). Heart rate (+3.62 bpm; p = 0.009), mean arterial pressure (+4.14 mmHg; p = 0.033), central diastolic blood pressure (+4.16 mmHg; p = 0.038), and peripheral diastolic blood pressure (+4.09 mmHg; p = 0.044) also significantly increased during hyperglycemic-hyperinsulinemia. CONCLUSIONS Hyperglycemic-hyperinsulinemia acutely increased cfPWV, heart rate, mean arterial pressure, and diastolic blood pressure in healthy humans, perhaps reflecting enhanced sympathetic tone. Whether repeated bouts of hyperglycemia with hyperinsulinemia contribute to chronically-enhanced arterial stiffness remains unknown.
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Affiliation(s)
- William B Horton
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Linda A Jahn
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Lee M Hartline
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Kevin W Aylor
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - James T Patrie
- Division of Biostatistics, Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Eugene J Barrett
- Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA
- Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA, USA
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14
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Park JJ. Epidemiology, Pathophysiology, Diagnosis and Treatment of Heart Failure in Diabetes. Diabetes Metab J 2021; 45:146-157. [PMID: 33813813 PMCID: PMC8024162 DOI: 10.4093/dmj.2020.0282] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 02/25/2021] [Indexed: 12/11/2022] Open
Abstract
The cardiovascular disease continuum begins with risk factors such as diabetes mellitus (DM), progresses to vasculopathy and myocardial dysfunction, and finally ends with cardiovascular death. Diabetes is associated with a 2- to 4-fold increased risk for heart failure (HF). Moreover, HF patients with DM have a worse prognosis than those without DM. Diabetes can cause myocardial ischemia via micro- and macrovasculopathy and can directly exert deleterious effects on the myocardium. Hyperglycemia, hyperinsulinemia, and insulin resistance can cause alterations in vascular homeostasis. Then, reduced nitric oxide and increased reactive oxygen species levels favor inflammation leading to atherothrombotic progression and myocardial dysfunction. The classification, diagnosis, and treatment of HF for a patient with and without DM remain the same. Until now, drugs targeting neurohumoral and metabolic pathways improved mortality and morbidity in HF with reduced ejection fraction (HFrEF). Therefore, all HFrEF patients should receive guideline-directed medical therapy. By contrast, drugs modulating neurohumoral activity did not improve survival in HF with preserved ejection fraction (HFpEF) patients. Trials investigating whether sodium-glucose cotransporter-2 inhibitors are effective in HFpEF are on-going. This review will summarize the epidemiology, pathophysiology, and treatment of HF in diabetes.
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Affiliation(s)
- Jin Joo Park
- Cardiovascular Center, Division of Cardiology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
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15
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The Protective Effects of Ropivacaine Against High Glucose-induced Brain Microvascular Endothelial Injury by Reducing MMPs and Alleviating Oxidative Stress. Neurotox Res 2021; 39:851-859. [PMID: 33538995 DOI: 10.1007/s12640-020-00324-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 11/27/2020] [Accepted: 12/08/2020] [Indexed: 10/22/2022]
Abstract
Diabetes is undoubtedly affecting global health. Considerable attention has been directed to brain complications caused by diabetes, which are reported to be related to the injury on brain microvascular endothelial cells. Oxidative stress and degradation of vascular basement membrane contribute to the injury of vascular endothelia by diabetes. The present study aims to investigate the effects of ropivacaine on high glucose-induced brain microvascular endothelial injury, as well as the underlying mechanism. Cell viability was determined by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The production of reactive oxygen species (ROS) was evaluated by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. Quantitative real-time PCR (QRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to determine the expression levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), intercellular cell adhesion molecule-1 (ICAM-1), and vascular endothelial growth factor (VEGF). The production of nitric oxide (NO) was detected by DAF-FM DA staining. The expression of inducible nitric oxide synthase (iNOS) was evaluated by qRT-PCR and Western blot analysis. Western blot was used to determine the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1).The cell viability of bEnd.3 brain endothelial cells was inhibited by high glucose, which was rescued by ropivacaine. The elevated production of ROS and MDA by high glucose was reversed by ropivacaine. Ropivacaine suppressed the expression of up-regulated iNOS, NO, MMP-2, MMP-9, ICAM-1, and VEGF induced by high glucose incubation. The expression of Nrf-2 and HO-1 by high glucose incubation was significantly inhibited by ropivacaine treatment.Ropivacaine might alleviate high glucose-induced brain microvascular endothelial injury by suppressing oxidative stress and down-regulating MMPs.
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16
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Beck L, Pinilla E, Arcanjo DDR, Hernanz R, Prat-Duran J, Petersen AG, Köhler R, Sheykhzade M, Comerma-Steffensen S, Simonsen U. Pirfenidone Is a Vasodilator: Involvement of K V7 Channels in the Effect on Endothelium-Dependent Vasodilatation in Type-2 Diabetic Mice. Front Pharmacol 2021; 11:619152. [PMID: 33643042 PMCID: PMC7906977 DOI: 10.3389/fphar.2020.619152] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 12/30/2020] [Indexed: 12/27/2022] Open
Abstract
Endothelial cell dysfunction and fibrosis are associated with worsening of the prognosis in patients with cardiovascular disease. Pirfenidone has a direct antifibrotic effect, but vasodilatation may also contribute to the effects of pirfenidone. Therefore, in a first study we investigated the mechanisms involved in the relaxant effect of pirfenidone in rat intrapulmonary arteries and coronary arteries from normal mice. Then in a second study, we investigated whether pirfenidone restores endothelial function in the aorta and mesenteric arteries from diabetic animals. From 16–18-week old normal male C57BL/6 mice and normoglycemic (db/db+), and type 2 diabetic (db/db) male and female mice, arteries were mounted in microvascular isometric myographs for functional studies, and immunoblotting was performed. In rat pulmonary arteries and mouse coronary arteries, pirfenidone induced relaxations, which were inhibited in preparations without endothelium. In mouse coronary arteries, pirfenidone relaxation was inhibited in the presence of a nitric oxide (NO) synthase inhibitor, NG-nitro-l-arginine (L-NOARG), a blocker of large-conductance calcium-activated potassium channels (BKCa), iberiotoxin, and a blocker of KV7 channels, XE991. Patch clamp studies in vascular smooth muscle revealed pirfenidone increased iberiotoxin-sensitive current. In the aorta and mesenteric small arteries from diabetic db/db mice relaxations induced by the endothelium-dependent vasodilator, acetylcholine, were markedly reduced compared to db/db + mice. Pirfenidone enhanced the relaxations induced by acetylcholine in the aorta from diabetic male and female db/db mice. An opener of KV7 channels, flupirtine, had the same effect as pirfenidone. XE991 reduced the effect of pirfenidone and flupirtine and further reduced acetylcholine relaxations in the aorta. In the presence of iberiotoxin, pirfenidone still increased acetylcholine relaxation in aorta from db/db mice. Immunoblotting for KV7.4, KV7.5, and BKCa channel subunits were unaltered in aorta from db/db mice. Pirfenidone failed to improve acetylcholine relaxation in mesenteric arteries, and neither changed acetylcholine-induced transient decreases in blood pressure in db/db+ and db/db mice. In conclusion, pirfenidone vasodilates pulmonary and coronary arteries. In coronary arteries from normal mice, pirfenidone induces NO-dependent vasodilatation involving BKCa and KV7 channels. Pirfenidone improves endothelium-dependent vasodilatation in aorta from diabetic animals by a mechanism involving voltage-gated KV7 channels, a mechanism that may contribute to the antifibrotic effect of pirfenidone.
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Affiliation(s)
- Lilliana Beck
- Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Aarhus University, Aarhus, Denmark
| | - Estéfano Pinilla
- Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Aarhus University, Aarhus, Denmark.,Department of Physiology, Faculty of Pharmacy, Universidad Complutense, Madrid, Spain
| | - Daniel Dias Rufino Arcanjo
- Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Aarhus University, Aarhus, Denmark.,Department of Biophysics and Physiology, Laboratory of Functional and Molecular Studies in Physiopharmacology, Federal University of Piauí, Teresina, Brazil
| | - Raquel Hernanz
- Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Aarhus University, Aarhus, Denmark.,Departamento de Ciencias Básicas de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain
| | - Judit Prat-Duran
- Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Aarhus University, Aarhus, Denmark
| | - Asbjørn Graver Petersen
- Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Aarhus University, Aarhus, Denmark
| | - Ralf Köhler
- Aragón Agency for Research and Development (ARAID), Zaragoza, Spain
| | - Majid Sheykhzade
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Simon Comerma-Steffensen
- Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Aarhus University, Aarhus, Denmark.,Department of Biomedical Sciences/Animal Physiology, Faculty of Veterinary, Central University of Venezuela, Maracay, Venezuela
| | - Ulf Simonsen
- Department of Biomedicine, Pulmonary and Cardiovascular Pharmacology, Aarhus University, Aarhus, Denmark
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17
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Parker L, Morrison DJ, Wadley GD, Shaw CS, Betik AC, Roberts‐Thomson K, Kaur G, Keske MA. Prior exercise enhances skeletal muscle microvascular blood flow and mitigates microvascular flow impairments induced by a high‐glucose mixed meal in healthy young men. J Physiol 2020; 599:83-102. [DOI: 10.1113/jp280651] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Accepted: 10/09/2020] [Indexed: 01/11/2023] Open
Affiliation(s)
- Lewan Parker
- Institute for Physical Activity and Nutrition (IPAN) School of Exercise and Nutrition Sciences Deakin University Geelong Australia
| | - Dale J. Morrison
- Institute for Physical Activity and Nutrition (IPAN) School of Exercise and Nutrition Sciences Deakin University Geelong Australia
| | - Glenn D. Wadley
- Institute for Physical Activity and Nutrition (IPAN) School of Exercise and Nutrition Sciences Deakin University Geelong Australia
| | - Christopher S. Shaw
- Institute for Physical Activity and Nutrition (IPAN) School of Exercise and Nutrition Sciences Deakin University Geelong Australia
| | - Andrew C. Betik
- Institute for Physical Activity and Nutrition (IPAN) School of Exercise and Nutrition Sciences Deakin University Geelong Australia
| | - Katherine Roberts‐Thomson
- Institute for Physical Activity and Nutrition (IPAN) School of Exercise and Nutrition Sciences Deakin University Geelong Australia
| | - Gunveen Kaur
- Institute for Physical Activity and Nutrition (IPAN) School of Exercise and Nutrition Sciences Deakin University Geelong Australia
| | - Michelle A. Keske
- Institute for Physical Activity and Nutrition (IPAN) School of Exercise and Nutrition Sciences Deakin University Geelong Australia
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18
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Horton WB, Jahn LA, Hartline LM, Aylor KW, Patrie JT, Barrett EJ. Hyperglycemia does not Inhibit Insulin's Effects on Microvascular Perfusion in Healthy Humans: A Randomized Crossover Study. Am J Physiol Endocrinol Metab 2020; 319:E753-E762. [PMID: 32830553 DOI: 10.1152/ajpendo.00300.2020] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Diabetes mellitus accelerates vascular disease through multiple biochemical pathways driven by hyperglycemia, with insulin resistance and/or hyperinsulinemia also contributing. Persons with diabetes mellitus experience premature large vessel and microvascular disease when compared to normoglycemic controls. Currently there is a paucity of clinical data identifying how acutely the vasculature responds to hyperglycemia and whether other physiologic factors (e.g., vasoactive hormones) contribute. To our knowledge, no prior studies have examined the dynamic effects of acute hyperglycemia on insulin-mediated actions on both micro- and macrovascular function in the same subjects. In this randomized crossover trial, healthy young adults underwent two infusion protocols designed to compare the effects of insulin infusion during euglycemia and hyperglycemia on micro- and macrovascular function. Both euglycemic- and hyperglycemic-hyperinsulinemia increased skeletal (but not cardiac) muscle microvascular blood volume (each p<0.02) and blood flow significantly (each p<0.04), and these increases did not differ between protocols. Hyperglycemic-hyperinsulinemia trended towards increased carotid-femoral pulse wave velocity (indicating increased aortic stiffness; p= 0.065 after Bonferroni adjustment), while euglycemic-hyperinsulinemia did not. There were no changes in post-ischemic flow velocity or brachial artery flow-mediated dilation during either protocol. Plasma endothelin-1 levels significantly decreased during both protocols (each p<0.02). In this study, acute hyperglycemia for 4 hours did not inhibit insulin's ability to increase skeletal muscle microvascular perfusion but did provoke a slight increase in aortic stiffness. Hyperglycemia also did not adversely affect myocardial microvascular perfusion or endothelial function or prevent the decline of endothelin-1 during insulin infusion.
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Affiliation(s)
| | - Linda A Jahn
- endocrinology, University of Virginia, United States
| | | | - Kevin W Aylor
- Division of Endocrinology, Department of Medicine, Department of Pharmacology , University of Virginia, School of Medicine, Charlottesville, VA 22908; Department of Molecular and Clinical Medicine (
| | - James T Patrie
- Public Health Sciences, University of Virginia Medical Center, United States
| | - Eugene J Barrett
- Division of Endocrinology, Department of Medicine, Department of Pharmacology , University of Virginia, School of Medicine, Charlottesville, VA 22908; Department of Molecular and Clinical Medicine (, United States
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19
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Mason SA, Trewin AJ, Parker L, Wadley GD. Antioxidant supplements and endurance exercise: Current evidence and mechanistic insights. Redox Biol 2020; 35:101471. [PMID: 32127289 PMCID: PMC7284926 DOI: 10.1016/j.redox.2020.101471] [Citation(s) in RCA: 122] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 02/11/2020] [Accepted: 02/17/2020] [Indexed: 01/07/2023] Open
Abstract
Antioxidant supplements are commonly consumed by endurance athletes to minimize exercise-induced oxidative stress, with the intention of enhancing recovery and improving performance. There are numerous commercially available nutritional supplements that are targeted to athletes and health enthusiasts that allegedly possess antioxidant properties. However, most of these compounds are poorly investigated with respect to their in vivo redox activity and efficacy in humans. Therefore, this review will firstly provide a background to endurance exercise-related redox signalling and the subsequent adaptations in skeletal muscle and vascular function. The review will then discuss commonly available compounds with purported antioxidant effects for use by athletes. N-acetyl cysteine may be of benefit over the days prior to an endurance event; while chronic intake of combined 1000 mg vitamin C + vitamin E is not recommended during periods of heavy training associated with adaptations in skeletal muscle. Melatonin, vitamin E and α-lipoic acid appear effective at decreasing markers of exercise-induced oxidative stress. However, evidence on their effects on endurance performance are either lacking or not supportive. Catechins, anthocyanins, coenzyme Q10 and vitamin C may improve vascular function, however, evidence is either limited to specific sub-populations and/or does not translate to improved performance. Finally, additional research should clarify the potential benefits of curcumin in improving muscle recovery post intensive exercise; and the potential hampering effects of astaxanthin, selenium and vitamin A on skeletal muscle adaptations to endurance training. Overall, we highlight the lack of supportive evidence for most antioxidant compounds to recommend to athletes.
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Affiliation(s)
- Shaun A Mason
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia
| | - Adam J Trewin
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia
| | - Lewan Parker
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia
| | - Glenn D Wadley
- Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia.
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20
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Smiljanec K, Mbakwe AU, Ramos-Gonzalez M, Pohlig RT, Lennon SL. Antioxidant cocktail following a high-sodium meal does not affect vascular function in young, healthy adult humans: a randomized controlled crossover trial. Nutr Res 2020; 79:13-22. [PMID: 32610254 DOI: 10.1016/j.nutres.2020.05.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 05/06/2020] [Accepted: 05/18/2020] [Indexed: 02/06/2023]
Abstract
Chronic high sodium intake is a risk factor for cardiovascular disease as it impairs vascular function through an increase in oxidative stress. The objective of this study was to investigate the acute effects of a high-sodium meal (HSM) and antioxidant (AO) cocktail on vascular function. We hypothesized that a HSM would impair endothelial function, and increase arterial stiffness and wave reflection, while ingestion of the AO cocktail would mitigate this response. Healthy adults ingested either an AO cocktail (vitamin C, E, alpha-lipoic acid) or placebo (PLA) followed by a HSM (1500 mg) in a randomized crossover blinded design. Blood pressure (BP), endothelial function (flow-mediated dilation; FMD) and measures of arterial stiffness (pulse wave velocity; PWV) and wave reflection (augmentation index; AIx) were made at baseline and 30, 60, 90, and 120 min after meal consumption. Forty-one participants (20M/21W; 24 ± 1 years; BMI 23.4 ± 0.4 kg/m2) completed the study. Mean BP increased at 120 min relative to 60 min (60 min: 79 ± 1; 120 min: 81 ± 1 mmHg; time effect P = .01) but was not different between treatments (treatment × time interaction P = .32). AIx decreased from baseline (time effect P < .001) but was not different between treatments (treatment × time interaction P = .31). PWV (treatment × time interaction, P = .91) and FMD (treatment × time interaction P = .65) were also not different between treatments. In conclusion, a HSM does not acutely impair vascular function suggesting young healthy adults can withstand the acute impact of sodium on the vasculature and therefore, the AO cocktail is not necessary to mitigate the response.
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Affiliation(s)
- Katarina Smiljanec
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE.
| | - Alexis U Mbakwe
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE.
| | | | - Ryan T Pohlig
- Biostatistics Core Facility, University of Delaware, STAR, Newark, DE.
| | - Shannon L Lennon
- Department of Kinesiology and Applied Physiology, University of Delaware, Newark, DE.
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21
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Pharmacology and perspectives in erectile dysfunction in man. Pharmacol Ther 2020; 208:107493. [PMID: 31991196 DOI: 10.1016/j.pharmthera.2020.107493] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Accepted: 11/05/2019] [Indexed: 12/15/2022]
Abstract
Penile erection is a perfect example of microcirculation modulated by psychological factors and hormonal status. It is the result of a complex neurovascular process that involves the integrative synchronized action of vascular endothelium; smooth muscle; and psychological, neuronal, and hormonal systems. Therefore, the fine coordination of these events is essential to maintain penile flaccidity or allow erection; an alteration of these events leads to erectile dysfunction (ED). ED is defined as the consistent or recurrent inability of a man to attain and/or maintain a penile erection sufficient for sexual activity. A great boost to this research field was given by commercialization of phosphodiesterase-5 (PDE5) inhibitors. Indeed, following the discovery of sildenafil, research on the mechanisms underlying penile erection has had an enormous boost, and many preclinical and clinical papers have been published in the last 10 years. This review is structured to provide an overview of the mediators and peripheral mechanism(s) involved in penile function in men, the drugs used in therapy, and the future prospective in the management of ED. Indeed, 30% of patients affected by ED are classified as "nonresponders," and there is still an unmet need for therapeutic alternatives. A flowchart suggesting the guidelines for ED evaluation and the ED pharmacological treatment is also provided.
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22
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Muggeridge DJ, Goszcz K, Treweeke A, Adamson J, Hickson K, Crabtree D, Megson IL. Co-ingestion of Antioxidant Drinks With an Unhealthy Challenge Meal Fails to Prevent Post-prandial Endothelial Dysfunction: An Open-Label, Crossover Study in Older Overweight Volunteers. Front Physiol 2019; 10:1293. [PMID: 31681007 PMCID: PMC6797614 DOI: 10.3389/fphys.2019.01293] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 09/25/2019] [Indexed: 12/16/2022] Open
Abstract
Eating a high calorie meal is known to induce endothelial dysfunction and it is reported that consuming drinks rich in antioxidants may be protective against this. In this study we assessed the effects of three antioxidant drinks with considerable disparity in their antioxidant content on endothelial function. Seven apparently healthy overweight and older adults (BMI 25-35; mean age 57 ± 3 years; one male, six females) completed four trials in a randomized counterbalanced design. Water (control), orange juice, green tea, or red wine were consumed with a high calorie meal (>900 kcal). Endothelial function was measured by flow-mediated dilatation immediately before (fasted, baseline) and 2 h after the meal. Blood samples were also obtained for lipid and glucose analysis, plasma nitrite ( NO 2 - ) and oxidized low-density lipoprotein (ox-LDL). Participants returned after a minimum 3 days washout to complete the remaining arms of the study. The results found that the high calorie meal induced a substantial increase in triglycerides, but not cholesterol or glucose, at 2 h after meal ingestion. FMD was significantly reduced by ∼35% at this timepoint, but the effect was not attenuated by co-ingestion of any of the antioxidant drinks. Reduced FMD was mirrored by a reduction in NO 2 - , but ox-LDL was not increased at 2 h after the meal. None of the undertaken measures were influenced by the antioxidant drinks. We conclude that co-ingestion of none of our test antioxidant drinks protected against the substantial post-prandial endothelial dysfunction induced by an unhealthy meal challenge in our sample population at a 2 h timepoint.
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Affiliation(s)
- David J. Muggeridge
- Free Radical Research Facility, Division of Biomedical Sciences, Institute of Health Research and Innovation, University of the Highlands and Islands, Inverness, United Kingdom
- Active Health Exercise Laboratory, Division of Biomedical Sciences, Institute of Health Research and Innovation, University of the Highlands and Islands, Inverness, United Kingdom
| | - Katarzyna Goszcz
- Free Radical Research Facility, Division of Biomedical Sciences, Institute of Health Research and Innovation, University of the Highlands and Islands, Inverness, United Kingdom
| | - Andrew Treweeke
- Free Radical Research Facility, Division of Biomedical Sciences, Institute of Health Research and Innovation, University of the Highlands and Islands, Inverness, United Kingdom
| | - Janet Adamson
- Free Radical Research Facility, Division of Biomedical Sciences, Institute of Health Research and Innovation, University of the Highlands and Islands, Inverness, United Kingdom
| | - Kirsty Hickson
- Free Radical Research Facility, Division of Biomedical Sciences, Institute of Health Research and Innovation, University of the Highlands and Islands, Inverness, United Kingdom
- Active Health Exercise Laboratory, Division of Biomedical Sciences, Institute of Health Research and Innovation, University of the Highlands and Islands, Inverness, United Kingdom
| | - Daniel Crabtree
- Active Health Exercise Laboratory, Division of Biomedical Sciences, Institute of Health Research and Innovation, University of the Highlands and Islands, Inverness, United Kingdom
| | - Ian L. Megson
- Free Radical Research Facility, Division of Biomedical Sciences, Institute of Health Research and Innovation, University of the Highlands and Islands, Inverness, United Kingdom
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23
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Haspula D, Vallejos AK, Moore TM, Tomar N, Dash RK, Hoffmann BR. Influence of a Hyperglycemic Microenvironment on a Diabetic Versus Healthy Rat Vascular Endothelium Reveals Distinguishable Mechanistic and Phenotypic Responses. Front Physiol 2019; 10:558. [PMID: 31133884 PMCID: PMC6524400 DOI: 10.3389/fphys.2019.00558] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 04/24/2019] [Indexed: 12/18/2022] Open
Abstract
Hyperglycemia is a critical factor in the development of endothelial dysfunction in type 2 diabetes mellitus (T2DM). Whether hyperglycemic states result in a disruption of similar molecular mechanisms in endothelial cells under both diabetic and non-diabetic states, remains largely unknown. This study aimed to address this gap in knowledge through molecular and functional characterization of primary rat cardiac microvascular endothelial cells (RCMVECs) derived from the T2DM Goto-Kakizaki (GK) rat model in comparison to control Wistar-Kyoto (WKY) in response to a normal (NG) and hyperglycemic (HG) microenvironment. GK and WKY RCMVECs were cultured under NG (4.5 mM) and HG (25 mM) conditions for 3 weeks, followed by tandem mass spectrometry (MS/MS), qPCR, tube formation assay, microplate based fluorimetry, and mitochondrial respiration analyses. Following database matching and filtering (false discovery rate ≤ 5%, scan count ≥ 10), we identified a greater percentage of significantly altered proteins in GK (7.1%, HG versus NG), when compared to WKY (3.5%, HG versus NG) RCMVECs. Further stringent filters (log2ratio of > 2 or < -2, p < 0.05) followed by enrichment and pathway analyses of the MS/MS and quantitative PCR datasets (84 total genes screened), resulted in the identification of several molecular targets involved in angiogenic, redox and metabolic functions that were distinctively altered in GK as compared to WKY RCMVECs following HG exposure. While the expression of thirteen inflammatory and apoptotic genes were significantly increased in GK RCMVECs under HG conditions (p < 0.05), only 2 were significantly elevated in WKY RCMVECs under HG conditions. Several glycolytic enzymes were markedly reduced and pyruvate kinase activity was elevated in GK HG RCMVECs, while in mitochondrial respiratory chain activity was altered. Supporting this, TNFα and phorbol ester (PMA)-induced Reactive Oxygen Species (ROS) production were significantly enhanced in GK HG RCMVECs when compared to baseline levels (p < 0.05). Additionally, PMA mediated increase was the greatest in GK HG RCMVECs (p < 0.05). While HG caused reduction in tube formation assay parameters for WKY RCMVECs, GK RCMVECs exhibited impaired phenotypes under baseline conditions regardless of the glycemic microenvironment. We conclude that hyperglycemic microenvironment caused distinctive changes in the bioenergetics and REDOX pathways in the diabetic endothelium as compared to those observed in a healthy endothelium.
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Affiliation(s)
- Dhanush Haspula
- Department of Biomedical Engineering, Medical College of Wisconsin, Marquette University, Milwaukee, WI, United States.,Max McGee National Research Center, Children's Research Institute, Milwaukee, WI, United States
| | - Andrew K Vallejos
- Department of Biomedical Engineering, Medical College of Wisconsin, Marquette University, Milwaukee, WI, United States.,Clinical and Translational Science Institute, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Timothy M Moore
- Department of Biomedical Engineering, Medical College of Wisconsin, Marquette University, Milwaukee, WI, United States
| | - Namrata Tomar
- Department of Biomedical Engineering, Medical College of Wisconsin, Marquette University, Milwaukee, WI, United States
| | - Ranjan K Dash
- Department of Biomedical Engineering, Medical College of Wisconsin, Marquette University, Milwaukee, WI, United States.,Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Brian R Hoffmann
- Department of Biomedical Engineering, Medical College of Wisconsin, Marquette University, Milwaukee, WI, United States.,Max McGee National Research Center, Children's Research Institute, Milwaukee, WI, United States.,Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, United States.,Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI, United States.,Center for Advancing Population Science, Medical College of Wisconsin, Milwaukee, WI, United States
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24
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Sood R, Sharma D, Goel H, Khattar N, Kulshreshtha B, Singh KK. The correlation between erectile dysfunction and metabolic syndrome in an Indian population: A cross-sectional observational study. Arab J Urol 2019; 17:221-227. [PMID: 31489239 PMCID: PMC6711110 DOI: 10.1080/2090598x.2019.1600990] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/04/2018] [Indexed: 11/17/2022] Open
Abstract
Objective: To evaluate the relationship between erectile dysfunction (ED), based on the five-item International Index of Erectile Function questionnaire (IIEF-5), and presence of metabolic syndrome (MetS) or its components based on Adult Treatment Panel III guidelines. We also explored the impact of increasing insulin resistance (IR), as calculated using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) equation, on severity of ED. Pathophysiological links between ED and testosterone were re-evaluated. Patients and methods: In all, 357 patients with ED were evaluated; 53 patients with primary, psychogenic, surgical, post-traumatic or drug-induced ED were excluded. The remaining 304 patients were evaluated after obtaining written informed consent. The Institutional Review Board approved the study. We assessed comorbidities, IIEF-5 scores, lower urinary tract symptoms (LUTS) based on International Prostate Symptom Score (IPSS), blood sugars, lipid and hormonal profiles, and vitamin D3 levels. Further evaluation was done when indicated. Results: In all, 171 patients had MetS and 134 had pre-existing comorbidities (diabetes mellitus, 58; hypertension, 73; coronary artery disease, 13). The mean (SD) age was 44.6 (9.21) years and IIEF-5 score was 13.81 (3.17). ED severity was significantly correlated with presence of MetS. On multivariate analysis, there were significant correlations between ED and waist circumference, serum triglycerides, and fasting blood sugar. There was a statistically significant positive correlation between serum testosterone and IIEF-5 score (r = +0.292). The mean (SD) IR value (using the HOMA-IR formula) was 2.64 (2.87), which was statistically and negatively correlated with IIEF-5 scores (r = – 0.398). Receiver operating characteristic analysis showed that an IIEF-5 score of <14 predicted MetS and a HOMA-IR value of >2.1778 predicted MetS.
Conclusion: MetS or its components were present in 56.25% of the patients. Therefore presence of ED merits further evaluation for presence of MetS. This may help to prevent catastrophic and life-threatening consequences of MetS. Abbreviations: BMI: body mass index; CRP: C-reactive protein; CVD: cardiovascular disease; DBP: diastolic blood pressure; DM: diabetes mellitus; ED: erectile dysfunction; FBS: fasting blood sugar; HDL: high-density lipoprotein; HOMA-IR- Homeostatic Model Assessment for Insulin Resistance; HTN: hypertension; IIEF-5: five-item version of the International Index of Erectile Function; IR: insulin resistance; LDL: low-density lipoprotein; LUTS: lower Urinary Tract Symptoms; MetS: metabolic syndrome; NO: nitric oxide; OR: odds ratio; PPBS: post-prandial blood sugar; ROC: receiver operating characteristic; SBP: systolic blood pressure; TG: triglyceride; WC: waist circumference
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Affiliation(s)
- Rajeev Sood
- Department of Urology and Renal Transplant, Pgimer and Dr RML Hospital, New Delhi, India
| | - Dushiant Sharma
- Department of Urology and Renal Transplant, Pgimer and Dr RML Hospital, New Delhi, India
| | - Hemant Goel
- Department of Urology and Renal Transplant, Pgimer and Dr RML Hospital, New Delhi, India
| | - Nikhil Khattar
- Department of Urology and Renal Transplant, Pgimer and Dr RML Hospital, New Delhi, India
| | - Bindu Kulshreshtha
- Department of Endocrinology, Pgimer and Dr RML Hospital, New Delhi, India
| | - Kunal K Singh
- Department of Urology and Renal Transplant, Pgimer and Dr RML Hospital, New Delhi, India
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25
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Measurement and Clinical Significance of Lipid Peroxidation as a Biomarker of Oxidative Stress: Oxidative Stress in Diabetes, Atherosclerosis, and Chronic Inflammation. Antioxidants (Basel) 2019; 8:antiox8030072. [PMID: 30934586 PMCID: PMC6466575 DOI: 10.3390/antiox8030072] [Citation(s) in RCA: 295] [Impact Index Per Article: 49.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 03/19/2019] [Accepted: 03/20/2019] [Indexed: 12/17/2022] Open
Abstract
Endothelial dysfunction is one of the initial steps in the pathogenesis of atherosclerosis and development of cardiovascular disease in patients with diabetes mellitus. Several risk factors are associated with endothelial dysfunction and atherosclerosis, such as hypertension, dyslipidaemia, inflammation, oxidative stress, and advanced glycation-end products. Among these risk factors, oxidative stress is the largest contributor to the formation of atherosclerotic plaques. Measurement of reactive oxygen species (ROS) is still difficult, and assays for the measurement of ROS have failed to show a consistent correlation between pathological states and oxidative stress. To solve this problem, this review summarizes the current knowledge on biomarkers of oxidative stress, especially lipid peroxidation, and discusses the roles of oxidative stress, as measured by indices of lipid peroxidation, in diabetes mellitus, atherosclerosis, and chronic inflammation.
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26
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Duflot T, Moreau-Grangé L, Roche C, Iacob M, Wils J, Rémy-Jouet I, Cailleux AF, Leuillier M, Renet S, Li D, Morisseau C, Lamoureux F, Richard V, Prévost G, Joannidès R, Bellien J. Altered bioavailability of epoxyeicosatrienoic acids is associated with conduit artery endothelial dysfunction in type 2 diabetic patients. Cardiovasc Diabetol 2019; 18:35. [PMID: 30885203 PMCID: PMC6423843 DOI: 10.1186/s12933-019-0843-z] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 03/08/2019] [Indexed: 01/04/2023] Open
Abstract
Background This pathophysiological study addressed the hypothesis that soluble epoxide hydrolase (sEH), which metabolizes the vasodilator and anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), contributes to conduit artery endothelial dysfunction in type 2 diabetes. Methods and results Radial artery endothelium-dependent flow-mediated dilatation in response to hand skin heating was reduced in essential hypertensive patients (n = 9) and type 2 diabetic subjects with (n = 19) or without hypertension (n = 10) compared to healthy subjects (n = 36), taking into consideration cardiovascular risk factors, flow stimulus and endothelium-independent dilatation to glyceryl trinitrate. Diabetic patients but not non-diabetic hypertensive subjects displayed elevated whole blood reactive oxygen species levels and loss of NO release during heating, assessed by measuring local plasma nitrite variation. Moreover, plasma levels of EET regioisomers increased during heating in healthy subjects, did not change in hypertensive patients and decreased in diabetic patients. Correlation analysis showed in the overall population that the less NO and EETs bioavailability increases during heating, the more flow-mediated dilatation is reduced. The expression and activity of sEH, measured in isolated peripheral blood mononuclear cells, was elevated in diabetic but not hypertensive patients, leading to increased EETs conversion to DHETs. Finally, hyperglycemic and hyperinsulinemic euglycemic clamps induced a decrease in flow-mediated dilatation in healthy subjects and this was associated with an altered EETs release during heating. Conclusions These results demonstrate that an increased EETs degradation by sEH and altered NO bioavailability are associated with conduit artery endothelial dysfunction in type 2 diabetic patients independently from their hypertensive status. The hyperinsulinemic and hyperglycemic state in these patients may contribute to these alterations. Trial registration NCT02311075. Registered December 8, 2014. Electronic supplementary material The online version of this article (10.1186/s12933-019-0843-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Thomas Duflot
- Department of Pharmacology, Rouen University Hospital, 76000, Rouen Cedex, France.,Normandie Univ, UNIROUEN, INSERM U1096, FHU REMOD-VHF, 76000, Rouen, France.,Laboratory of Pharmacokinetics, Toxicology and Pharmacogenetics, Rouen University Hospital, 76000, Rouen, France
| | | | - Clothilde Roche
- Normandie Univ, UNIROUEN, INSERM U1096, FHU REMOD-VHF, 76000, Rouen, France
| | - Michèle Iacob
- Department of Pharmacology, Rouen University Hospital, 76000, Rouen Cedex, France
| | - Julien Wils
- Department of Pharmacology, Rouen University Hospital, 76000, Rouen Cedex, France.,Normandie Univ, UNIROUEN, INSERM U1096, FHU REMOD-VHF, 76000, Rouen, France
| | | | | | - Matthieu Leuillier
- Normandie Univ, UNIROUEN, INSERM U1096, FHU REMOD-VHF, 76000, Rouen, France
| | - Sylvanie Renet
- Normandie Univ, UNIROUEN, INSERM U1096, FHU REMOD-VHF, 76000, Rouen, France
| | - Dongyang Li
- Department of Entomology and Nematology, and Comprehensive Cancer Center, University of California, Davis, Davis, CA, 95616, USA
| | - Christophe Morisseau
- Department of Entomology and Nematology, and Comprehensive Cancer Center, University of California, Davis, Davis, CA, 95616, USA
| | - Fabien Lamoureux
- Department of Pharmacology, Rouen University Hospital, 76000, Rouen Cedex, France.,Normandie Univ, UNIROUEN, INSERM U1096, FHU REMOD-VHF, 76000, Rouen, France.,Laboratory of Pharmacokinetics, Toxicology and Pharmacogenetics, Rouen University Hospital, 76000, Rouen, France
| | - Vincent Richard
- Department of Pharmacology, Rouen University Hospital, 76000, Rouen Cedex, France.,Normandie Univ, UNIROUEN, INSERM U1096, FHU REMOD-VHF, 76000, Rouen, France
| | - Gaëtan Prévost
- Department of Endocrinology, Rouen University Hospital, 76000, Rouen, France.,Normandie Univ, UNIROUEN, INSERM U1239, 76000, Rouen, France
| | - Robinson Joannidès
- Department of Pharmacology, Rouen University Hospital, 76000, Rouen Cedex, France.,Normandie Univ, UNIROUEN, INSERM U1096, FHU REMOD-VHF, 76000, Rouen, France.,Centre d'Investigation Clinique (CIC)-INSERM 1404, Rouen University Hospital, 76000, Rouen, France
| | - Jérémy Bellien
- Department of Pharmacology, Rouen University Hospital, 76000, Rouen Cedex, France. .,Normandie Univ, UNIROUEN, INSERM U1096, FHU REMOD-VHF, 76000, Rouen, France. .,Centre d'Investigation Clinique (CIC)-INSERM 1404, Rouen University Hospital, 76000, Rouen, France.
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27
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Yasuda S, Goda M, Shibuya T, Uchida K, Suzuki S, Noishiki Y, Yokoyama U, Ishikawa Y, Masuda M. An appropriately sized soft polyester external stent prevents enlargement and neointimal hyperplasia of a saphenous vein graft in a canine model. Artif Organs 2019; 43:577-583. [DOI: 10.1111/aor.13399] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Revised: 11/06/2018] [Accepted: 11/20/2018] [Indexed: 12/21/2022]
Affiliation(s)
- Shota Yasuda
- Department of Surgery Yokohama City University Yokohama Japan
| | - Motohiko Goda
- Department of Surgery Yokohama City University Yokohama Japan
| | - Taisuke Shibuya
- Department of Surgery Yokohama City University Yokohama Japan
| | - Keiji Uchida
- Cardiovascular Center Yokohama City University Medical Center Yokohama Japan
| | - Shinichi Suzuki
- Department of Surgery Yokohama City University Yokohama Japan
| | - Yasuharu Noishiki
- Department of Neurological Anatomy Yokohama City University Yokohama Japan
| | - Utako Yokoyama
- Cardiovascular Research Institute Yokohama City University Yokohama Japan
| | - Yoshihiro Ishikawa
- Cardiovascular Research Institute Yokohama City University Yokohama Japan
| | - Munetaka Masuda
- Department of Surgery Yokohama City University Yokohama Japan
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28
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Co-ingestion of antioxidant drinks with an unhealthy challenge meal fails to prevent post-prandial endothelial dysfunction: an open-label, crossover study in healthy older adults. Proc Nutr Soc 2019. [DOI: 10.1017/s0029665119000314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Mehanna OM, El Askary A, Al-Shehri S, El-Esawy B. Effect of phosphodiesterase inhibitors on renal functions and oxidant/antioxidant parameters in streptozocin-induced diabetic rats. Arch Physiol Biochem 2018; 124:424-429. [PMID: 29271249 DOI: 10.1080/13813455.2017.1419267] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The goal of this study was to investigate the effect of different phosphodiesterase inhibitors (PDEIs), on renal oxidant/antioxidant balance in diabetic rats. Our study was conducted on 125 rats, diabetes was induced in 100 rats by a single administration of streptozocin (STZ). Diabetic rats were divided into four equal groups. The first group was assigned as diabetic control, the remaining three groups were treated with pentoxifylline, sildenafil and milrinone via drinking water for 15 successive days, another group of 25 normal rats was assigned as non-diabetic control. Significant increase in plasma levels of glucose, urea, creatinine, malondialdehyde (MDA), and nitric oxide (NO) with a concomitant decrease in the levels of insulin, reduced glutathione (GSH), glutathione peroxidase (Gpx), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAC) were observed in diabetic rats. These alterations were reverted back to near normal level after treatment with PDEIs. Our data seem to suggest a potential role of PDEIs in maintaining health in diabetes by reducing the progression of diabetic nephropathy.
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Affiliation(s)
- Osama Mahmoud Mehanna
- a Department of Medical Physiology, Faculty of Medicine , Taif University , Taif , KSA
- b Department of Medical Physiology, Faculty of Medicine (New Damietta) , Al-Azhar University , Cairo , Egypt
| | - Ahmad El Askary
- c Department of Clinical Laboratory Sciences, College of Applied Medical Sciences , Taif University , Taif , KSA
- d Department of Medical Biochemistry, Faculty of Medicine (New Damietta) , Al-Azhar University , Cairo , Egypt
| | - Saad Al-Shehri
- c Department of Clinical Laboratory Sciences, College of Applied Medical Sciences , Taif University , Taif , KSA
| | - Basem El-Esawy
- c Department of Clinical Laboratory Sciences, College of Applied Medical Sciences , Taif University , Taif , KSA
- e Department of Pathology, Faculty of medicine , Mansoura University , Mansoura , Egypt
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30
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Rezaei N, Mardanshahi T, Shafaroudi MM, Abedian S, Mohammadi H, Zare Z. Effects of l-Carnitine on the Follicle-Stimulating Hormone, Luteinizing Hormone, Testosterone, and Testicular Tissue Oxidative Stress Levels in Streptozotocin-Induced Diabetic Rats. J Evid Based Integr Med 2018; 23:2515690X18796053. [PMID: 30168346 PMCID: PMC6120171 DOI: 10.1177/2515690x18796053] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The present study was designed to investigate the antioxidant property of l-carnitine (LC) on serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (TH) and testis oxidative stress in streptozotocin (STZ)-induced diabetic rats. The rats were divided into the following groups: group I, control; group II, LC 100 mg/kg/d; group III, diabetic; and groups IV to VI, diabetic rats treated with 50, 100, and 200 mg/kg/d of LC, respectively. Daily injections were given intraperitoneally for 7 weeks. At the end of experimental period, after sacrificing the rats, FSH, LH, TH, total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), mitochondrial function (MTT), protein carbonyl (PC), and reactive oxygen species (ROS) levels were measured. STZ caused an elevation of MDA, ROS, and PC (P < .001) with reduction of GSH, CAT, TAC, and MTT (P < .001) in the serum levels. Group VI had significantly increased FSH, LH, and TH levels versus the untreated diabetic group (P < .001). Although groups V and VI significantly decreased MDA (P < .001), PC (P < .01), and ROS (P < .01) compared with the untreated diabetic group; only in group VI, the activity of GSH (P < .001), CAT (P < .01), TAC (P < .001), and MTT (P < .001) significantly increased. The results of the present study suggest that LC decreased diabetes-induced oxidative stress complications and also improved serum level of FSH, LH, and TH by reducing levels of lipid peroxidation and increasing antioxidant enzymes.
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Affiliation(s)
| | | | | | - Saeed Abedian
- 1 Mazandaran University of Medical Sciences, Sari, Iran
| | | | - Zohre Zare
- 1 Mazandaran University of Medical Sciences, Sari, Iran
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Effect of Intermittent Energy Restriction on Flow Mediated Dilatation, a Measure of Endothelial Function: A Short Report. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2018; 15:ijerph15061166. [PMID: 29867034 PMCID: PMC6025364 DOI: 10.3390/ijerph15061166] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Revised: 05/25/2018] [Accepted: 06/01/2018] [Indexed: 01/27/2023]
Abstract
Intermittent energy restriction is a popular alternative to daily energy restriction for weight loss; however, it is unknown if endothelial function, a risk factor for cardiovascular disease, is altered by periods of severe energy restriction. The objective of the study was to determine the impact of two consecutive very low energy intake days, which is the core component of the 5:2 intermittent energy restriction diet strategy, on endothelial function compared to consecutive ad libitum eating days. The secondary objective was to explore the effects of these dietary conditions on fasting glucose concentrations. This was a 4-week randomized, single-blinded, crossover study of 35 participants. Participants consumed a very low energy diet (500 calories for women, 600 calories for men) on two consecutive days per week and 5 days of habitual eating. In weeks 3 and 4 of the trial, participants had measurements of flow mediated dilatation (FMD) and blood samples taken following either 2 habitual eating days or 2 energy restricted days in a randomized order. FMD values were not different after the two eating states (8.6% vs. 8.3%, p = 0.7). All other outcome variables were unchanged. Endothelial function, as measured by flow mediated dilatation, was not altered by two consecutive very low energy intake days. Further investigations assessing the impact in specific population groups as well as different testing conditions would be beneficial.
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Das EK, Lai PY, Robinson AT, Pleuss J, Ali MM, Haus JM, Gutterman DD, Phillips SA. Regular Aerobic, Resistance, and Cross-Training Exercise Prevents Reduced Vascular Function Following a High Sugar or High Fat Mixed Meal in Young Healthy Adults. Front Physiol 2018; 9:183. [PMID: 29568273 PMCID: PMC5853082 DOI: 10.3389/fphys.2018.00183] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Accepted: 02/20/2018] [Indexed: 01/19/2023] Open
Abstract
The postprandial state can negatively influence flow mediated dilation (FMD), a predictor of atherosclerosis and cardiovascular disease. This investigation was designed to determine the effect of regular aerobic and/or resistance exercise on postprandial FMD after a high sugar or high fat mixed meal. Forty-five healthy participants were recruited from one of four groups: lean sedentary (SED), runners, weight lifters, and cross-trainers. Participants were randomly crossed over to a high sugar meal (HSM) and a high fat mixed meal (HFMM; both fat and carbohydrate). Pre-and postprandial endothelial function was assessed for both meals using brachial artery FMD. Plasma lipids, insulin, glucose, hs-CRP, and SOD were also measured with both meals. Endothelium-independent dilation was determined via sublingual nitroglycerin. Brachial artery FMD was reduced in SED following the HSM (9.9 ± 0.9% at baseline, peak reduction at 60 min 6.5 ± 1.0%) and the HFMM (9.4 ± 0.9% at baseline, peak reduction at 120 min 5.9 ± 1.2%; P < 0.05 for both, Mean ± SEM). There was no change in FMD after either HSM or HFMM in runners, weight lifters, and cross-trainers. Post-prandial increases in blood glucose, insulin and triglycerides were less pronounced in the exercisers compared to SED. In addition, exercisers presented lower baseline plasma hs-CRP and higher SOD activity. Nitroglycerin responses were similar among groups. These results suggest that endothelial function is reduced in sedentary adults after a HSM or HFMM, but not in regular aerobic or resistance exercisers. This response may be due to favorable postprandial metabolic responses or lower postprandial levels of inflammation and oxidative stress. These findings may help to explain the cardioprotective effect of exercise.
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Affiliation(s)
- Emon K Das
- Department of Medicine, Cardiovascular Center and Clinical Research Center, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Pui Y Lai
- Department of Medicine, Cardiovascular Center and Clinical Research Center, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Austin T Robinson
- Department of Physical Therapy, University of Illinois, Chicago, IL, United States.,Department of Kinesiology and Nutrition, University of Illinois, Chicago, IL, United States.,Integrative Physiology Laboratory, University of Illinois, Chicago, IL, United States
| | - Joan Pleuss
- Department of Medicine, Cardiovascular Center and Clinical Research Center, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Mohamed M Ali
- Department of Physical Therapy, University of Illinois, Chicago, IL, United States.,Department of Kinesiology and Nutrition, University of Illinois, Chicago, IL, United States.,Integrative Physiology Laboratory, University of Illinois, Chicago, IL, United States
| | - Jacob M Haus
- Department of Kinesiology and Nutrition, University of Illinois, Chicago, IL, United States.,Integrative Physiology Laboratory, University of Illinois, Chicago, IL, United States
| | - David D Gutterman
- Department of Medicine, Cardiovascular Center and Clinical Research Center, Medical College of Wisconsin, Milwaukee, WI, United States
| | - Shane A Phillips
- Department of Medicine, Cardiovascular Center and Clinical Research Center, Medical College of Wisconsin, Milwaukee, WI, United States.,Department of Physical Therapy, University of Illinois, Chicago, IL, United States.,Department of Kinesiology and Nutrition, University of Illinois, Chicago, IL, United States.,Integrative Physiology Laboratory, University of Illinois, Chicago, IL, United States.,Department of Medicine, University of Illinois, Chicago, IL, United States
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Perez de la Hoz RA, Swieszkowski SP, Cintora FM, Aladio JM, Papini CM, Matsudo M, Scazziota AS. Neuroendocrine System Regulatory Mechanisms: Acute Coronary Syndrome and Stress Hyperglycaemia. Eur Cardiol 2018; 13:29-34. [PMID: 30310467 DOI: 10.15420/ecr.2017:19:3] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Neurohormonal systems are activated in the early phase of acute coronary syndromes to preserve circulatory homeostasis, but prolonged action of these stress hormones might be deleterious. Cortisol reaches its peak at 8 hours after the onset of symptoms, and individuals who have continued elevated levels present a worse prognosis. Catecholamines reach 100-1,000-fold their normal plasma concentration within 30 minutes of ischaemia, therefore inducing the propagation of myocardial damage. Stress hyperglycaemia induces inflammation and endothelial dysfunction, and also has procoagulant and prothrombotic effects. Patients with hyperglycaemia and no diabetes elevated in-hospital and 12-month mortality rates. Hyperglycaemia in patients without diabetes has been shown to be an appropriate independent mortality prognostic factor in this type of patient.
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Affiliation(s)
| | | | | | | | | | - Maia Matsudo
- School of Medicine, Buenos Aires University Buenos Aires, Argentina
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Conflicting effects of atazanavir therapy on atherosclerotic risk factors in stable HIV patients: A randomized trial of regimen switch to atazanavir. PLoS One 2017; 12:e0181993. [PMID: 29023508 PMCID: PMC5638209 DOI: 10.1371/journal.pone.0181993] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2017] [Accepted: 07/06/2017] [Indexed: 12/29/2022] Open
Abstract
Bilirubin acts as a potent endogenous antioxidant, with higher concentrations associated with lower rates of CVD; the antiretroviral drug atazanavir (ATV) increases bilirubin levels but may also increase von Willebrand factor levels. We tested the hypothesis that increasing endogenous bilirubin using ATV would improve cardiometabolic risk factors and vascular function in older patients with HIV. Ninety participants were enrolled in two study protocols. In protocol 1, we evaluated markers of inflammation, thrombosis, and conduit artery endothelial function in subjects on non-ATV containing regimens. Participants were randomly assigned to continue baseline treatment or switch to an ATV-based regimen. Measurements were made at baseline and 28 days. In the protocol 2, we enrolled 30 subjects who received atazanavir for more than one year and were compared to the aim 1 protocol subjects at baseline. 60 subjects were enrolled in the first protocol (mean age 53, +/- 6 years), with 31 randomized to ATV and 29 continuing baseline treatment. Atazanavir significantly increased serum total bilirubin levels (p<0.001) and acutely but not chronically plasma total antioxidant capacity (p<0.001). An increase in von Willebrand Factor (p<0.001) and reduction in hs-CRP (p = 0.034) were noted. No changes were seen in either flow-mediated endothelium-dependent or vasodilation. In cross-sectional analysis (second protocol), similar findings were seen in the baseline attributes of non-atazanavir-based and long-term atazanavir users. Increasing serum bilirubin levels with atazanavir in subjects with HIV reduces hs-CRP, temporarily reduces oxidative stress, but increases von Willebrand Factor. Atazanavir does not improve endothelial function of conduit arteries. Trial registration: ClinicalTrials.gov NCT03019783.
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Ebert TJ, Novalija J, Barney JA, Uhrich TD, Arain SR, Freed JK, Pagel PS. Moderate, Short-Term, Local Hyperglycemia Attenuates Forearm Endothelium-Dependent Vasodilation After Transient Ischemia-Reperfusion in Human Volunteers. J Cardiothorac Vasc Anesth 2017; 31:1649-1655. [DOI: 10.1053/j.jvca.2016.11.040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2016] [Indexed: 01/08/2023]
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Goszcz K, Duthie GG, Stewart D, Leslie SJ, Megson IL. Bioactive polyphenols and cardiovascular disease: chemical antagonists, pharmacological agents or xenobiotics that drive an adaptive response? Br J Pharmacol 2017; 174:1209-1225. [PMID: 28071785 PMCID: PMC5429332 DOI: 10.1111/bph.13708] [Citation(s) in RCA: 95] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Revised: 12/19/2016] [Accepted: 01/05/2017] [Indexed: 12/12/2022] Open
Abstract
Polyphenols are widely regarded to have a wide range of health-promoting qualities, including beneficial effects on cardiovascular disease. Historically, the benefits have been linked to their well-recognized powerful antioxidant activity. However, the concept that the beneficial effects are attributable to direct antioxidant activity in vivo does not pay sufficient heed to the fact that polyphenols degrade rapidly, are poorly absorbed and rapidly metabolized, resulting in very low bioavailability. This review explores alternative mechanisms by which polyphenols, or their metabolites, exert biological activity via mechanisms that can be activated by physiologically relevant concentrations. Evidence is presented to support the action of phenolic derivatives on receptors and signalling pathways to induce adaptive responses that drive changes in endogenous antioxidant, antiplatelet, vasodilatory and anti-inflammatory effects. The implications are that in vitro antioxidant measures as predictors of polyphenol protective activity in vivo hold little relevance and that closer attention needs to be paid to bioavailable metabolites to understand the mode of action of these diet-derived components. LINKED ARTICLES This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.
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Affiliation(s)
- Katarzyna Goszcz
- Department of Diabetes and Cardiovascular ScienceUniversity of the Highlands and Islands, Centre for Health ScienceInvernessUK
| | - Garry G Duthie
- Rowett Institute of Nutrition and HealthUniversity of AberdeenAberdeenUK
| | - Derek Stewart
- The James Hutton InstituteDundeeUK
- School of Engineering and Physical SciencesHeriot‐Watt UniversityEdinburghUK
| | - Stephen J Leslie
- Department of Diabetes and Cardiovascular ScienceUniversity of the Highlands and Islands, Centre for Health ScienceInvernessUK
- Cardiology UnitRaigmore HospitalInvernessUK
| | - Ian L Megson
- Department of Diabetes and Cardiovascular ScienceUniversity of the Highlands and Islands, Centre for Health ScienceInvernessUK
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Vorn R, Yoo HY. Effects of high glucose with or without other metabolic substrates on alpha-adrenergic contractions in rat mesenteric and femoral arteries. THE KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY : OFFICIAL JOURNAL OF THE KOREAN PHYSIOLOGICAL SOCIETY AND THE KOREAN SOCIETY OF PHARMACOLOGY 2016; 21:91-97. [PMID: 28066145 PMCID: PMC5214915 DOI: 10.4196/kjpp.2017.21.1.91] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Revised: 10/04/2016] [Accepted: 10/10/2016] [Indexed: 01/01/2023]
Abstract
Hyperglycemia is associated with an increased risk of cardiovascular diseases. It has been demonstrated that chronic exposure to high glucose impaired endothelial functions. However, specific effects of short-term exposure to high glucose on vascular reactivity are controversial. Moreover, the combined effects of other metabolic substrates such as free fatty acids (FFA) on vascular reactivity remain poorly understood. Here we investigate the effects of short-term exposure to high glucose with or without other metabolic substrates including FFAs termed “nutrition full” (NF) solution, on mesenteric (MA) and deep femoral arteries (DFA) of rats. Arterial ring segments were mounted in a double-wire myograph. Contraction in response to phenylephrine (PhE) was determined in control (5 mM) and high glucose (23 mM, HG) environments over a 30 min period. In both arteries, PhE-inducedvasocontraction was enhanced by pre-incubation of HG solution. A combined incubation with HG and palmitic acid (100 µM) induced similar sensitization of PhE-contractions in both arteries. In contrast, high K+-induced contractions were not affected by HG. Interestingly, pre-incubation with NF solution decreased PhE-induced contraction in MA but increased the contraction in DFA. In NF solution, the HG-induced facilitation of PhE-contraction was not observed in MA. Furthermore, the PhE-induced contraction of DFA was attenuated by HG in NF solution. Our results demonstrate that the sensitization of PhE-induced arterial contraction by HG is differentially affected by other metabolic substrates. The conversation of skeletal arterial contractility by HG in NF solution requires careful interpretation of the previous in vitro studies where only glucose is included in physiological salt solutions. Further studies are required to elucidate the mechanism underlying the inconsistent effect of NF solution on MA and DFA.
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Affiliation(s)
- Rany Vorn
- Chung-Ang University Red Cross College of Nursing, Seoul 06974, Korea.; Chung-Ang University Graduate School, Seoul 06974, Korea
| | - Hae Young Yoo
- Chung-Ang University Red Cross College of Nursing, Seoul 06974, Korea
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Luo P, Li R, Yu S, Xu T, Yue S, Ji Y, Chen X, Xie H. The Relationship between Neutrophil-to-Lymphocyte Ratio and Intracerebral Hemorrhage in Type 2 Diabetes Mellitus. J Stroke Cerebrovasc Dis 2016; 26:930-937. [PMID: 27908556 DOI: 10.1016/j.jstrokecerebrovasdis.2016.10.041] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2016] [Revised: 10/26/2016] [Accepted: 10/31/2016] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Chronic systematic inflammation has been suggested to be associated with the occurrence and development of cardiovascular events. Low-grade systematic inflammation persists in type 2 diabetes mellitus (T2DM) patients. In addition, the risk of cerebral hemorrhage in these patients is increased compared with non-diabetic patients. Neutrophil-to-lymphocyte ratio (NLR) is the ratio derived by dividing the neutrophil count with the lymphocyte count from a peripheral blood sample. This study aimed to explore the relation between NLR and cerebral hemorrhage, and to prove that NLR is an independent risk factor of cerebral hemorrhage in T2DM patients. METHODS In total, 429 cases of T2DM patients were included. The patients were divided into two groups depending on the presence of cerebral hemorrhage: the cerebral hemorrhage group (n = 87) and the control group (n = 342). Based on clinical and laboratory data of diabetes diagnosis, this article investigates the relationship between NLR and the risk of cerebral hemorrhage. RESULTS Increase in NLR was positively correlated with the incidence of cerebral hemorrhage in T2DM patients and might serve as an independent risk factor of cerebral hemorrhage in T2DM patients (OR: 4.451, 95% CI: 2.582-7.672). NLR >2.58 might be useful in predicting the threshold value of cerebral hemorrhage risk in newly diagnosed T2DM patients (area under the curve: .72, 95% CI: .659-.780, P < .001) CONCLUSION: As an indicator of the degree of systematic inflammation, NLR is an independent risk factor of cerebral hemorrhage in T2DM patients.
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Affiliation(s)
- Peng Luo
- Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Rui Li
- Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Siyuan Yu
- Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Tingting Xu
- Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Shufan Yue
- Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Yongli Ji
- Zhujiang Hospital, Southern Medical University, Guangzhou, China
| | - Xin Chen
- Zhujiang Hospital, Southern Medical University, Guangzhou, China.
| | - Haiting Xie
- Zhujiang Hospital, Southern Medical University, Guangzhou, China.
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Abstract
Atypical hemolytic-uremic syndrome (HUS) is a rare life-threatening disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and ischemic injury to organs, especially the kidneys. Microvascular injury and thrombosis are the dominant histologic findings. Complement activation through the alternative pathway plays a critical role in the pathogenesis of atypical HUS. Genetic abnormalities involving complement regulatory proteins and complement components form the molecular basis for complement activation. Endothelial cell dysfunction, probably because of the effects of complement activation, is an intermediate stage in the pathophysiologic cascade. Atypical HUS has a grave prognosis. Although mortality approaches 25% during the acute phase, end-stage renal disease develops in nearly half of patients within a year. Atypical HUS has a high recurrence rate after renal transplantation, and recurrent disease often leads to graft loss. Plasma therapy in the form of plasma exchange or infusion has remained the standard treatment for atypical HUS. However, many patients do not respond to plasma therapy and some require prolonged treatment. Approved by the Food and Drug Administration in the treatment of atypical HUS, eculizumab is a humanized monoclonal antibody that blocks cleavage of complement C5 into biologically active mediators of inflammation and cytolysis. Although case reports have shown the efficacy of eculizumab, randomized clinical trials are lacking. Therapeutic strategies targeting endothelial cells have demonstrated promising results in experimental settings. Therefore, inhibitors of angiotensin-converting enzyme, HMG-CoA reductase, and xanthine oxidase as well as antioxidants, such as ascorbic acid, may have salutary effects in patients with atypical HUS.
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Beckman JA, Goldfine AB, Leopold JA, Creager MA. Ebselen does not improve oxidative stress and vascular function in patients with diabetes: a randomized, crossover trial. Am J Physiol Heart Circ Physiol 2016; 311:H1431-H1436. [PMID: 27765750 DOI: 10.1152/ajpheart.00504.2016] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 10/05/2016] [Indexed: 12/18/2022]
Abstract
Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione peroxidase mimetic. A single-site, randomized, double-masked, placebo-controlled, crossover trial was carried out in 26 patients with type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg po twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 wk duration, with a 4-wk washout between treatments. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced to oxidized glutathione. Vascular ultrasound of the brachial artery and plethysmographic measurement of blood flow were used to assess flow-mediated and methacholine-induced endothelium-dependent vasodilation of conduit and resistance vessels, respectively. Ebselen administration did not affect parameters of oxidative stress or conduit artery or forearm arteriolar vascular function compared with placebo treatment. There was no difference in outcome by diabetes type. Ebselen, at the dose and duration evaluated, does not improve the oxidative stress profile, nor does it affect endothelium-dependent vasodilation in patients with diabetes mellitus.
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Affiliation(s)
- Joshua A Beckman
- Cardiovascular Division, Vanderbilt University Medical Center, Nashville, Tennessee;
| | - Allison B Goldfine
- Clinical, Behavioral and Outcomes Research, Joslin Diabetes Center, Boston, Massachusetts
| | - Jane A Leopold
- Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts; and
| | - Mark A Creager
- Heart and Vascular Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
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Abdel-Ghani M, El-Sherry T, Hayder M, Abou-Khalil N. Profile of peroxidative injury and antioxidant indicators in singleton, twins and multiple bearing goats throughout pregnancy. ASIAN PACIFIC JOURNAL OF REPRODUCTION 2016. [DOI: 10.1016/j.apjr.2016.07.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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Padayatty SJ, Levine M. Vitamin C: the known and the unknown and Goldilocks. Oral Dis 2016; 22:463-93. [PMID: 26808119 PMCID: PMC4959991 DOI: 10.1111/odi.12446] [Citation(s) in RCA: 426] [Impact Index Per Article: 47.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2016] [Accepted: 01/08/2016] [Indexed: 12/11/2022]
Abstract
Vitamin C (Ascorbic Acid), the antiscorbutic vitamin, cannot be synthesized by humans and other primates, and has to be obtained from diet. Ascorbic acid is an electron donor and acts as a cofactor for fifteen mammalian enzymes. Two sodium-dependent transporters are specific for ascorbic acid, and its oxidation product dehydroascorbic acid is transported by glucose transporters. Ascorbic acid is differentially accumulated by most tissues and body fluids. Plasma and tissue vitamin C concentrations are dependent on amount consumed, bioavailability, renal excretion, and utilization. To be biologically meaningful or to be clinically relevant, in vitro and in vivo studies of vitamin C actions have to take into account physiologic concentrations of the vitamin. In this paper, we review vitamin C physiology; the many phenomena involving vitamin C where new knowledge has accrued or where understanding remains limited; raise questions about the vitamin that remain to be answered; and explore lines of investigations that are likely to be fruitful.
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Affiliation(s)
- S J Padayatty
- Molecular and Clinical Nutrition Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - M Levine
- Molecular and Clinical Nutrition Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
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Administration of tauroursodeoxycholic acid prevents endothelial dysfunction caused by an oral glucose load. Clin Sci (Lond) 2016; 130:1881-8. [PMID: 27503949 DOI: 10.1042/cs20160501] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Accepted: 08/08/2016] [Indexed: 12/13/2022]
Abstract
Postprandial hyperglycaemia leads to a transient impairment in endothelial function; however, the mechanisms remain largely unknown. Previous work in cell culture models demonstrate that high glucose results in endoplasmic reticulum (ER) stress and, in animal studies, ER stress has been implicated as a cause of endothelial dysfunction. In the present study, we tested the hypothesis that acute oral administration of tauroursodeoxycholic acid (TUDCA, 1500 mg), a chemical chaperone known to alleviate ER stress, would prevent hyperglycaemia-induced endothelial dysfunction. In 12 young healthy subjects (seven men, five women), brachial artery flow-mediated dilation (FMD) was assessed at baseline, and at 60 and 120 min after an oral glucose challenge. Subjects were tested on two separate visits in a single-blind randomized cross-over design: after oral ingestion of TUDCA or placebo capsules. FMD was reduced from baseline during hyperglycaemia under the placebo condition (-32% at 60 min and -28% at 120 min post oral glucose load; P<0.05 from baseline) but not under the TUDCA condition (-4% at 60 min and +0.3% at 120 min post oral glucose load; P>0.05 from baseline). Postprandial plasma glucose and insulin were not altered by TUDCA ingestion. Plasma oxidative stress markers 3-nitrotyrosine and thiobarbituric acid reactive substance (TBARS) remained unaltered throughout the oral glucose challenge in both conditions. These results suggest that hyperglycaemia-induced endothelial dysfunction can be mitigated by oral administration of TUDCA, thus supporting the hypothesis that ER stress may contribute to endothelial dysfunction during postprandial hyperglycaemia.
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May JM. Ascorbic acid repletion: A possible therapy for diabetic macular edema? Free Radic Biol Med 2016; 94:47-54. [PMID: 26898503 PMCID: PMC4844774 DOI: 10.1016/j.freeradbiomed.2016.02.019] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Revised: 02/10/2016] [Accepted: 02/16/2016] [Indexed: 02/07/2023]
Abstract
Macular edema poses a significant risk for visual loss in persons with diabetic retinopathy. It occurs when plasma constituents and fluid leak out of damaged retinal microvasculature in the area of the macula, causing loss of central vision. Apoptotic loss of pericytes surrounding capillaries is perhaps the earliest feature of diabetic vascular damage in the macula, which is also associated with dysfunction of the endothelium and loss of the otherwise very tight endothelial permeability barrier. Increased oxidative stress is a key feature of damage to both cell types, mediated by excess superoxide from glucose-induced increases in mitochondrial metabolism, as well as by activation of the receptor for advanced glycation end products (RAGE). The latter in turn activates multiple pathways, some of which lead to increased oxidative stress, such as those involving NF-ĸB, NADPH oxidase, and endothelial nitric oxide synthase. Such cellular oxidative stress is associated with low cellular and plasma ascorbic acid levels in many subjects with diabetes in poor glycemic control. Whether repletion of low ascorbate in retinal endothelium and pericytes might help to prevent diabetic macular edema is unknown. However, cell culture studies show that the vitamin prevents high-glucose and RAGE-induced apoptosis in both cell types, that it preserves nitric oxide generated by endothelial cells, and that it tightens the leaky endothelial permeability barrier. Although these findings need to be confirmed in pre-clinical animal studies, it is worth considering clinical trials to determine whether adequate ascorbate repletion is possible and whether it might help to delay or even reverse early diabetic macular edema.
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Affiliation(s)
- James M May
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-6303, United States.
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Gomez-Arbelaez D, Sánchez-Vallejo G, Perez M, Garcia RG, Arguello JF, Peñaherrera E, Duarte YC, Casanova ME, Accini JL, Sotomayor A, Camacho PA, Lopez-Jaramillo P. [Hyperglycaemia is associated with worse outcomes in Latin-American individuals with acute myocardial infarction]. CLINICA E INVESTIGACION EN ARTERIOSCLEROSIS : PUBLICACION OFICIAL DE LA SOCIEDAD ESPANOLA DE ARTERIOSCLEROSIS 2016; 28:9-18. [PMID: 26596523 DOI: 10.1016/j.arteri.2015.09.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 09/15/2015] [Indexed: 06/05/2023]
Abstract
BACKGROUND Alterations in glucose metabolism have been reported as risk and poor prognostic factors for acute myocardial infarction (AMI); however in Latin-American population this information is limited. Thus, an evaluation was performed on the association between glycaemic status and short- and long-term outcomes in patients with a first AMI. METHODS A multicentre, prospective, observational, cohort study was conducted in 8 hospitals from Colombia and Ecuador. RESULTS A total of 439 patients with confirmed AMI were included, of which 305 (69.5%) had prediabetes or type2 diabetes mellitus (DM2). Compared with normal glycaemia group, patients with known DM2 had greater risk of prolonged hospital stay (HR: 2.60, 95%CI: 1.38-4.92, P=.003), Killip class iii/iv (HR: 9.46, 95%CI: 2.20-40.62, P=.002), and in-hospital heart failure (HR: 10.76, 95%CI: 3.37-34.31, P<.001). Patients with prediabetes, new DM2, and known DM2 showed higher rates of major adverse cardiovascular events after 3years follow-up. CONCLUSION Glucose metabolism abnormalities have an important significance in the short- and long-term prognosis in Latin-American patients that survive a first AMI.
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Affiliation(s)
- Diego Gomez-Arbelaez
- Fundación Oftalmológica de Santander-FOSCAL, Floridablanca, Colombia; Instituto de Investigaciones MASIRA, Facultad de Medicina, Universidad de Santander-UDES, Bucaramanga, Colombia; División de Endocrinología, Escuela de Medicina, Universidad de Santiago de Compostela, Santiago de Compostela, La Coruña, España
| | - Gregorio Sánchez-Vallejo
- Universidad del Quindío, Hospital San Juan de Dios, Fundación Cardiomet-Cequin, Armenia, Colombia
| | - Maritza Perez
- Departamento de Medicina Interna, Universidad Militar Nueva Granada, Bogotá, Colombia
| | - Ronald Gerardo Garcia
- Instituto de Investigaciones MASIRA, Facultad de Medicina, Universidad de Santander-UDES, Bucaramanga, Colombia; Fundación Cardiovascular de Colombia-FCV , Floridablanca, Colombia
| | | | | | | | | | - Jose Luis Accini
- Unidad de Cuidados Intensivos, Clínica Jaller, Universidad Libre, Barranquilla, Colombia
| | | | | | - Patricio Lopez-Jaramillo
- Fundación Oftalmológica de Santander-FOSCAL, Floridablanca, Colombia; Instituto de Investigaciones MASIRA, Facultad de Medicina, Universidad de Santander-UDES, Bucaramanga, Colombia.
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Milian J, Goldfine AB, Zuflacht JP, Parmer C, Beckman JA. Atazanavir improves cardiometabolic measures but not vascular function in patients with long-standing type 1 diabetes mellitus. Acta Diabetol 2015; 52:709-15. [PMID: 25563478 PMCID: PMC4496330 DOI: 10.1007/s00592-014-0708-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Accepted: 12/22/2014] [Indexed: 12/24/2022]
Abstract
AIMS Vascular disease is the leading cause of morbidity and mortality in type 1 diabetes mellitus (T1DM). We previously demonstrated that patients with T1DM have impaired endothelial function, a forme fruste of atherosclerosis, as a result of increased oxidative stress. Bilirubin has emerged as a potent endogenous antioxidant with higher concentrations associated with lower rates of myocardial infarction and stroke. METHODS We tested the hypothesis that increasing endogenous bilirubin using atazanavir would improve cardiometabolic risk factors and vascular function in patients with T1DM to determine whether targeting bilirubin may be a novel therapeutic approach to reduce cardiovascular disease risk in this population. In this single-arm, open-label study, we evaluated blood pressure, lipid profile, and conduit artery function in fifteen subjects (mean age 45 ± 9 years) with T1DM following a 4-day treatment with atazanavir. RESULTS As anticipated, atazanavir significantly increased both serum total bilirubin levels (p < 0.0001) and plasma total antioxidant capacity (p < 0.0001). Reductions in total cholesterol (p = 0.04), LDL cholesterol (p = 0.04), and mean arterial pressure (p = 0.04) were also observed following atazanavir treatment. No changes were seen in either flow-mediated endothelium-dependent (p = 0.92) or nitroglycerine-mediated endothelium-independent (p = 0.68) vasodilation, measured by high-resolution B-mode ultrasonography at baseline and post-treatment. CONCLUSION Increasing serum bilirubin levels with atazanavir in subjects with T1DM over 4 days favorably reduces LDL and blood pressure but is not associated with improvements in endothelial function of conduit arteries.
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Affiliation(s)
- Jessica Milian
- Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA
| | | | - Jonah P. Zuflacht
- Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA
| | - Caitlin Parmer
- Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA
| | - Joshua A. Beckman
- Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA
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Goszcz K, Deakin SJ, Duthie GG, Stewart D, Leslie SJ, Megson IL. Antioxidants in Cardiovascular Therapy: Panacea or False Hope? Front Cardiovasc Med 2015; 2:29. [PMID: 26664900 PMCID: PMC4671344 DOI: 10.3389/fcvm.2015.00029] [Citation(s) in RCA: 108] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 06/10/2015] [Indexed: 12/31/2022] Open
Abstract
Oxidative stress is a key feature of the atherothrombotic process involved in the etiology of heart attacks, ischemic strokes, and peripheral arterial disease. It stands to reason that antioxidants represent a credible therapeutic option to prevent disease progression and thereby improve outcome, but despite positive findings from in vitro studies, clinical trials have failed to consistently show benefit. The aim of this review is to re-appraise the concept of antioxidants in the prevention and management of cardiovascular disease. In particular, the review will explore the reasons behind failed antioxidant strategies with vitamin supplements and will evaluate how flavonoids might improve cardiovascular function despite bioavailability that is not sufficiently high to directly influence antioxidant capacity. As well as reaching conclusions relating to those antioxidant strategies that might hold merit, the major myths, limitations, and pitfalls associated with this research field are explored.
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Affiliation(s)
- Katarzyna Goszcz
- Department of Diabetes and Cardiovascular Science, Centre for Health Science, University of the Highlands and Islands , Inverness , UK ; James Hutton Institute , Dundee , UK
| | - Sherine J Deakin
- Department of Diabetes and Cardiovascular Science, Centre for Health Science, University of the Highlands and Islands , Inverness , UK
| | - Garry G Duthie
- Rowett Institute of Health and Nutrition , Aberdeen , UK
| | - Derek Stewart
- James Hutton Institute , Dundee , UK ; School of Life Sciences, Heriot Watt University , Edinburgh , UK
| | - Stephen J Leslie
- Department of Diabetes and Cardiovascular Science, Centre for Health Science, University of the Highlands and Islands , Inverness , UK ; Cardiology Unit, Raigmore Hospital , Inverness , UK
| | - Ian L Megson
- Department of Diabetes and Cardiovascular Science, Centre for Health Science, University of the Highlands and Islands , Inverness , UK
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Contribution of Musa paradisiaca in the inhibition of α-amylase, α-glucosidase and Angiotensin-I converting enzyme in streptozotocin induced rats. Life Sci 2015; 133:8-14. [DOI: 10.1016/j.lfs.2015.03.026] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2014] [Revised: 03/08/2015] [Accepted: 03/24/2015] [Indexed: 11/19/2022]
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Antioxidative diet supplementation reverses high-fat diet-induced increases of cardiovascular risk factors in mice. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2015; 2015:467471. [PMID: 25922641 PMCID: PMC4397488 DOI: 10.1155/2015/467471] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Revised: 03/15/2015] [Accepted: 03/16/2015] [Indexed: 01/09/2023]
Abstract
Obesity is a worldwide epidemic that is characterized not only by excessive fat deposition but also by systemic microinflammation, high oxidative stress, and increased cardiovascular risk factors. While diets enriched in natural antioxidants showed beneficial effects on oxidative stress, blood pressure, and serum lipid composition, diet supplementation with synthetic antioxidants showed contradictive results. Thus, we tested in C57Bl/6 mice whether a daily dosage of an antioxidative mixture consisting of vitamin C, vitamin E, L-arginine, eicosapentaenoic acid, and docosahexaenoic acid (corabion) would affect cardiovascular risk factors associated with obesity. Obese mice showed increased serum triglyceride and glucose levels and hypertension after eight weeks of being fed a high-fat diet (HFD). Importantly, corabion ameliorated all of these symptoms significantly. Oxidative stress and early signs of systemic microinflammation already developed after two weeks of high-fat diet and were significantly reduced by daily doses of corabion. Of note, the beneficial effects of corabion could not be observed when applying its single antioxidative components suggesting that a combination of various nutrients is required to counteract HFD-induced cardiovascular risk factors. Thus, daily consumption of corabion may be beneficial for the management of obesity-related cardiovascular complications.
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50
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Sanjay S, Bharti GS, Manish G, Rajeev P, Pankaj A, Puspalata A, Keshavkumar G. Metabolic syndrome: An independent risk factor for erectile dysfunction. Indian J Endocrinol Metab 2015; 19:277-282. [PMID: 25729692 PMCID: PMC4319270 DOI: 10.4103/2230-8210.149322] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
OBJECTIVE The objective was to determine the role of various components of metabolic syndrome (MetS) as independent risk factor for erectile dysfunction (ED). MATERIALS AND METHODS A total of 113 subjects of MetS, as recommended by recent IDF and AHA/NHLBI joint interim statement were selected for study who presented for ED. After doing Anthropometric examination, fasting laboratory assay for fasting plasma glucose (FPG), fasting insulin, hemoglobin A1c, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and 2 h oral glucose tolerance test (OGTT) was done. Erectile function was assessed by completing questions one through five of the International Index of Erectile Function (IIEF-5). A multiple linear regression analysis was carried out on 66 subjects with IIEF-5 score as dependent variable and components of MetS FPG, 2 h OGTT, TG, HDL, and waist circumference as independent variables. RESULTS Using a multiple linear regression analysis, we observed that presence of the various components of MetS was associated with ED and a decrease IIEF-5 score and this effect was greater than the effect associated with any of the individual components. Of the individual components of the MetS, HDL (B = 0.136; P = 0.004) and FPG (B = -0.069; P = 0.007) conferred the strongest effect on IIEF-5 score. However, overall age had most significant effect on IIEF-5 score. CONCLUSION It is crucial to formulate strategies and implement them to prevent or control the epidemic of the MetS and its consequences. The early identification and treatment of risk factors might be helpful to prevent ED and secondary cardiovascular disease, including diet and lifestyle interventions.
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Affiliation(s)
- Saran Sanjay
- Department of Endocrinology, LLRM Medical College, Meerut, India
| | | | - Gutch Manish
- Department of Endocrinology, LLRM Medical College, Meerut, India
| | - Philip Rajeev
- Department of Endocrinology, Pushpagiri Medical College Thiruvalla, Kerala
| | - Agrawal Pankaj
- Department of Endocrinology, Hormone Care and Research Centre, Ghaziabad, Uttar Pradesh, India
| | - Agroiya Puspalata
- Department of Ophthalmology, Subharti Medical College, Meerut, India
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