Abstract 18317: Activation of Autophagy Mediates Insulin-Like Growth Factor I (igf-1)-Induced Anti-Apoptotic Effect in Vascular Smooth Muscle Cells

Introduction: We have previously shown that smooth muscle cell (SMC)-specific IGF-1 receptor (IGF1R) deficiency enhances plaque SMC apoptosis and increases atherosclerosis in Apoe-null mice, however the underlying mechanism was not identified. Autophagy is a reparative process safeguarding plaque cells against oxidative injury, by degrading the damaged intracellular material. Hypothesis: We hypothesized that IGF-1-induced autophagy in SMC mediates IGF-1-induced anti-apoptotic effect. Methods: We isolated aortic SMC from floxed IGF-1R mice (control, FIR) and from SMC-specific IGF1R-null mice (22KI), and confirmed cell identity by staining for SMC markers α-SMA and calponin. 22KI SMC had increased cell-doubling time (22KI, 79±6h vs. FIR, 61±5h) and decreased cell proliferation (reduced EdU labeling). We quantified autophagy by measuring LC3-II (autophagy marker) levels (immunoblotting) and assessing autophagosome puncta number (Autophagy detection kit, Abcam) Results: Serum deprivation induced a ~2-fold inc...