Resveratrol Treatment Reduces Cardiac Progenitor Cell Dysfunction and Prevents Morpho-Functional Ventricular Remodeling in Type-1 Diabetic Rats
Open Access
- 29 June 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (6), e39836
- https://doi.org/10.1371/journal.pone.0039836
Abstract
Emerging evidence suggests that both adult cardiac cell and the cardiac stem/progenitor cell (CSPC) compartments are involved in the patho-physiology of diabetic cardiomyopathy (DCM). We evaluated whether early administration of Resveratrol, a natural antioxidant polyphenolic compound, in addition to improving cardiomyocyte function, exerts a protective role on (i) the progenitor cell pool, and (ii) the myocardial environment and its impact on CSPCs, positively interfering with the onset of DCM phenotype. Adult Wistar rats (n = 128) with streptozotocin-induced type-1 diabetes were either untreated (D group; n = 54) or subjected to administration of trans-Resveratrol (i.p. injection: 2.5 mg/Kg/day; DR group; n = 64). Twenty-five rats constituted the control group (C). After 1, 3 or 8 weeks of hyperglycemia, we evaluated cardiac hemodynamic performance, and cardiomyocyte contractile properties and intracellular calcium dynamics. Myocardial remodeling and tissue inflammation were also assessed by morphometry, immunohistochemistry and immunoblotting. Eventually, the impact of the diabetic “milieu” on CSPC turnover was analyzed in co-cultures of healthy CSPCs and cardiomyocytes isolated from D and DR diabetic hearts. In untreated animals, cardiac function was maintained during the first 3 weeks of hyperglycemia, although a definite ventricular remodeling was already present, mainly characterized by a marked loss of CSPCs and adult cardiac cells. Relevant signs of ventricular dysfunction appeared after 8 weeks of diabetes, and included: 1) a significant reduction in ±dP/dt in comparison with C group, 2) a prolongation of isovolumic contraction/relaxation times, 3) an impaired contraction of isolated cardiomyocytes associated with altered intracellular calcium dynamics. Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing inflammatory state and decreased unfavorable ventricular remodeling of the diabetic heart, leading to a marked recovery of ventricular function. These findings indicate that RSV can constitute an adjuvant therapeutic option in DCM prevention.Keywords
This publication has 54 references indexed in Scilit:
- Resveratrol in cardiovascular health and diseaseAnnals of the New York Academy of Sciences, 2011
- Resveratrol and cardiovascular healthMolecular Aspects of Medicine, 2010
- Quantification of trans-resveratrol and its metabolites in rat plasma and tissues by HPLCJournal of Pharmaceutical and Biomedical Analysis, 2010
- Akt Downregulation by Flavin Oxidase–Induced ROS Generation Mediates Dose-Dependent Endothelial Cell Damage Elicited by Natural AntioxidantsToxicological Sciences, 2009
- Resveratrol inhibits foam cell formation via NADPH oxidase 1-mediated reactive oxygen species and monocyte chemotactic protein-1Experimental & Molecular Medicine, 2009
- Resveratrol reduces infarct size and improves ventricular function after myocardial ischemia in ratsLife Sciences, 2008
- Oxidative Stress Triggers Cardiac Fibrosis in the Heart of Diabetic RatsEndocrinology, 2008
- High Mobility Group 1 Protein (Hmg-1) Stimulates Proinflammatory Cytokine Synthesis in Human MonocytesThe Journal of Experimental Medicine, 2000
- Alpha-skeletal actin is associated with increased contractility in the mouse heart.Circulation Research, 1994
- Assessment of left ventricular relaxation by Doppler echocardiography. Comparison of isovolumic relaxation time and transmitral flow velocities with time constant of isovolumic relaxation.Circulation, 1990