title: Red wine antioxidant resveratrol-modified cardiac stem cells regenerate infarcted myocardium.
abstract: To study the efficiency of maintaining the reduced tissue environment via pre-treatment with natural antioxidant resveratrol in stem cell therapy, we pre-treated male Sprague-Dawley rats with resveratrol (2.5 mg/kg/day gavaged for 2 weeks). After occlusion of the left anterior descending coronary artery (LAD), adult cardiac stem cells stably expressing EGFP were injected into the border zone of the myocardium. One week after the LAD occlusion, the cardiac reduced environment was confirmed in resveratrol-treated rat hearts by the enhanced expression of nuclear factor-E2-related factor-2 (Nrf2) and redox effector factor-1 (Ref-1). In concert, cardiac functional parameters (left ventricular ejection fraction and fractional shortening) were significantly improved. The improvement of cardiac function was accompanied by the enhanced stem cell survival and proliferation as demonstrated by the expression of cell proliferation marker Ki67 and differentiation of stem cells towards the regeneration of the myocardium as demonstrated by the enhanced expression of EGFP 28 days after LAD occlusion in the resveratrol-treated hearts. Our results demonstrate that resveratrol maintained a reduced tissue environment by overexpressing Nrf2 and Ref-1 in rats resulting in an enhancement of the cardiac regeneration of the adult cardiac stem cells as demonstrated by increased cell survival and differentiation leading to cardiac function.
authors: Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06030-1110, USA.
authors: Narasimman
authors: N
authors: Gurusamy
authors: Diptarka
authors: D
authors: Ray
authors: Istvan
authors: I
authors: Lekli
authors: Dipak K
authors: DK
authors: Das
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D054377:Chemokine CXCL12 / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006334:Heart Function Tests; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000187:drug effects*; D000077185:Resveratrol; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D014920:Wine
chemical_list: D000975:Antioxidants; D054377:Chemokine CXCL12; D013267:Stilbenes; D049452:Green Fluorescent Proteins; D000077185:Resveratrol