Insulin activates vascular endothelial growth factor in vascular smooth muscle cells: influence of nitric oxide and of insulin resistance

• DOI: 10.1111/j.1365-2362.2004.01412.x
• Publication Date: 2004-10-07T11:25:38Z
• Authors: G. Doronzo; I. Russo; L. Mattiello; G. Anfossi; A. Bosia; M. Trovati
• Keywords: Wortmannin; Sodium nitroprusside; Cyclic guanosine monophosphate; cGMP-dependent protein kinase

We aimed to evaluate whether insulin influences vascular endothelial growth factor (VEGF) synthesis and secretion in cultured smooth muscle cells (VSMCs) via nitric oxide (NO) these putative effects are lost insulin-resistant states.In VSMC derived from human arterioles aortas of insulin-sensitive Zucker fa/+rats fa/fa rats incubated with different concentrations regular or without inhibitors phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3-K), mitogen-activated protein kinase (MAPK), synthase (NOS) guanosine 3',5'cyclic monophosphate(cGMP)-dependent (PKG), we measured expression (Western blot) (ELISA) VEGF.We found that VSMCs humans fa/+rats, increases VEGF secretion, mechanisms blunted by wortmannin LY294002 (PI3-K inhibitors), PD98059 (MAPK inhibitor), L-NMMA (NOS inhibitor) Rp-8pCT-cGMPs (PKG inhibitor). Also the NO donor sodium nitroprusside (SNP) cGMP analogue 8-Bromo-cGMP increase inhibited PD98059. The on impaired rats, which also present a reduced ability NO.In fa/+rats: (i) both PI3-K MAPK; (ii) mediated oxide. action is an animal model metabolic insulin-resistance.