Abstract 15652: Insulin-Like Growth Factor-1 Induces Vascular Smooth Muscle Cell Contractile Phenotype via a PI3K-Mediated Post-Transcriptional Mechanism Dependent on the α5β1 Integrin

In the progression of atherosclerosis, remodeling of the vessel wall occurs in which the extracellular matrix environment is altered and smooth muscle cells (SMCs) undergo a loss of contractile phenotype leading to increased plaque vulnerability and propensity for aneurysm formation. Our earlier studies have shown that insulin-like growth factor-1 (IGF-1)-infusion or SMC-specific IGF-1 overexpression increases contractile SMCs in atherosclerotic plaques of ApoE-/- mice. To investigate signal transduction mechanisms whereby IGF-1 induces contractile protein expression, human aortic SMCs were cultured and treated with 0-100 ng/mL IGF-1 for 0-24 hours in the presence of various inhibitors. IGF-1 induced a dose-dependent increase in expression of SMC contractile proteins, alpha-actin (αSMA) and smooth muscle 22-alpha (SM22α) (~2-fold-increase each with 100 ng/mL, p<0.01, n=10), without affecting mRNA levels. Additionally, IGF-1-upregulation of αSMA and SM22α protein expression was not blocked by actinomycin D...