Abstract
Insulin-like growth factor-1 (IGF-1), elevated in response to injury, may play a pivotal role during lesion formation in atherosclerosis and post-angioplasty restenosis. We examined the effects of IGF-1 on human aortic SMC apoptosis using Annexin V labeling, ELISA for oligonucleosomes and electron microscopy. We also examined the expression of PKC isozymes by immunoblotting. We show that whereas serum withdrawal induced up to 2% apoptosis, the broad-spectrum PKC inhibitor staurosporine (STAU) induced up to 62% apoptosis. IGF-1 incompletely attenuated apoptosis in a dose-dependent manner, with a max effect occurring between 10-50ng/ml. In addition, human ASMCs express alpha, beta1, delta, epsilon and zeta PKC isozymes and IGF-1 (100ng/ml) dose-dependently increased PKC epsilon expression. STAU decreased PKC epsilon expression by 15-20 fold with the maximum effect at 24 hours. IGF-1 partially reversed the effect of STAU. Our preliminary data revealed that PKC epsilon antisense oligodeoxynucleotides effectively inhibited expression of this isozyme and partially reversed the IGF-1 induced effect These data suggest that PKC epsilon is important in the survival effects of IGF-1 in VSMCs.