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


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.


CONCLUSIONS
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.
Desouza
Cyrus V
CV
Omaha Veterans Affairs Medical Center, Omaha, NE 68105, USA. cdesouza@unmc.edu
Gerety
Moira
M
Hamel
Frederick G
FG
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006965:Hyperplasia / Q000188:drug therapy / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D047495:PPAR gamma / Q000819:agonists; D000077205:Pioglitazone; D051381:Rats; D011924:Rats, Zucker; D045162:Thiazolidinediones / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D042461:Vascular Endothelial Growth Factor A; D000077205:Pioglitazone