Effects of resveratrol on endothelial progenitor cells and their contributions to reendothelialization in intima-injured rats

J Cardiovasc Pharmacol. 2006 May;47(5):711-21. doi: 10.1097/01.fjc.0000211764.52012.e3.

Abstract

The aim of this study was to investigate the effects of resveratrol on endothelial progenitor cell (EPC) activities in vitro and on the mobilization of circulating EPCs, and reendothelialization in balloon-injured aorta of rats. After being isolated, cultured, and characterized, human EPCs were stimulated with resveratrol. We found that a low concentration of resveratrol (1 microM) led to significant enhanced activities of proliferation, migration, and adhesion, as well as promoting endothelial nitric acid synthetase (eNOS) expression in EPCs, whereas a high concentration (60 microM) inhibited the aforementioned functions and eNOS expression. In a rat model of injured aorta, a low dosage of resveratrol (10 mg/kg) increased the amount of EPCs in rat circulation as compared with placebo, whereas the result of a high dosage (50 mg/kg) did not reach statistical difference. In addition, 10 mg/kg of resveratrol both accelerated reendothelialization and inhibited neointimal formation; however, 50 mg/kg only reduced neointimal formation, which was not as effective as the previous one. eNOS expression in injured arteries was potently enhanced in the 10 mg/kg group, but not in the 50 mg/kg group. These findings suggest that a low dosage of resveratrol could markedly raise the proliferative, migrative, and adhesive activities of EPCs and upgrade eNOS expression in vitro as well as increase EPC mobilization, enhance eNOS expression, and accelerate the repair of injured artery; however, a high dosage cannot.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Aorta, Abdominal / drug effects
  • Aorta, Abdominal / injuries
  • Aorta, Abdominal / physiology
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / injuries
  • Aorta, Thoracic / physiology
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism
  • Humans
  • Male
  • Nitric Oxide Synthase Type III / biosynthesis*
  • Nitric Oxide Synthase Type III / genetics
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Resveratrol
  • Stem Cells / cytology
  • Stem Cells / drug effects*
  • Stem Cells / metabolism
  • Stilbenes / pharmacology*
  • Tunica Intima / drug effects
  • Tunica Intima / injuries
  • Tunica Intima / physiology
  • Up-Regulation

Substances

  • Angiogenesis Inhibitors
  • RNA, Messenger
  • Stilbenes
  • Nitric Oxide Synthase Type III
  • Resveratrol