Neointimal hyperplasia and vascular endothelial growth factor expression are increased in normoglycemic, insulin resistant, obese fatty rats.

Abstract

OBJECTIVE: Insulin resistance is associated with a constellation of factors that enhance the artherosclerotic process. Vessel injury results in the formation of a markedly increased neointima in type 2 diabetes. Increased neointimal hyperplasia (NH) and vascular endothelial growth factor (VEGF) expression may lead to restenosis post angioplasty. We studied NH and VEGF expression in an obese, insulin resistant, but normoglycemic rat model, after carotid balloon injury. METHODS AND RESULTS: Diabetic rats (ZDF, n=10), normoglycemic, insulin-resistant rats (ZDF-normoglycemic, n=6) as well as Zucker fatty rats (FZ, n=6), and lean Zucker rats (LZ, n=6), all 13-16 weeks old, were subjected to right carotid injury by an angioplasty catheter introduced via the femoral artery. Three weeks later the rats were sacrificed and serum and carotids obtained. The intima-media ratio (I/M) was then calculated. ZDF-normoglycemic, FZ and ZDF-diabetic rats were all hyperinsulinemic and hypertriglyceridemic when compared to LZ rats. ZDF diabetic rats were hyperglycemic while FZ, ZDF-normoglycemic and LZ rats were normoglycemic. The I/M ratio for ZDF and FZ rats were significantly greater than for LZ rats. The VEGF expression was significantly greater in ZDF and FZ rats than LZ rats. CONCLUSIONS: In conclusion, insulin resistance increases neointimal hyperplasia and VEGF expression even with normoglycemia, after carotid angioplasty in rats.