Long-term effects of a PPAR-gamma agonist, pioglitazone, on neointimal hyperplasia and endothelial regrowth in insulin resistant rats

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12 Scopus citations

Abstract

Objective: Insulin resistance is an independent risk factor for cardiovascular disease. PPAR-gamma agonists like pioglitazone decrease insulin resistance and have been shown to reduce neointimal hyperplasia in the short-term. However long-term studies on endothelial regrowth and neointimal hyperplasia have not been done. Methods and results: We used hyperinsulinemic, normoglycemic Zucker fatty rats. Rats were treated with either 10 mg/kg body wt. pioglitazone or placebo till the end of the experiment. Rats underwent carotid angioplasty at age 12-14 weeks, 1 week after treatment was begun. In one set of experiments rats were sacrificed at 6 months and neointimal hyperplasia and VEGF expression was assessed. In another set of experiments rats were sacrificed at 3 and 6 months. Endothelial regrowth was determined. The rats were all normoglycemic and hyperinsulinemic. Pioglitazone treated rats had a significantly lesser degree of neointimal hyperplasia than control rats. Treated rats also had decreased VEGF expression. Endothelial regrowth was decreased in the treated rats at 6 months. Conclusion: We conclude that although pioglitazone decreases neointimal hyperplasia even at 6 months, it retards endothelial regrowth, which could predispose the denuded vessel to thrombotic events. This may be modulated by a suppression of VEGF expression.

Original languageEnglish (US)
Pages (from-to)188-194
Number of pages7
JournalVascular Pharmacology
Volume46
Issue number3
DOIs
StatePublished - Mar 2007

Keywords

  • Endothelial regrowth
  • Insulin resistance
  • Neointimal hyperplasia
  • PPAR-gamma
  • Pioglitazone

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology

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