Abstract 4749: Sustained PI3K-Akt/PKB Phosphorylation Potentiates Proliferation of Human Saphenous Vein Smooth Muscle Cells
Coronary revascularization by coronary artery bypass grafting (CABG) is recommended in patients with recurrent myocardial ischemia. However, the long-term results of CABG using saphenous vein (SV) graft, as compared to internal mammary artery (IMA) graft, have not been satisfactory. The SV graft failure is due to development of intimal hyperplasia, a process characterized by abnormal migration and proliferation of smooth muscle cells (SMCs) in the intimal layer of the vein graft. IGF-1 is a major mitogenic growth factor released at the site of the shear stress-induced graft injury. This study, for the first time, compares the extent of IGF-1-PI3K-Akt/PKB activation in isolated human SV and IMA SMCs and ex-vivo SV and IMA tissue sections. Immunohistochemistry data demonstrated a temporally greater activation of PI3K and Akt/PKB following IGF-1 (100 ng/ml) stimulation in SV tissues than in the IMA. The data from the immunoblotting and CASE assay demonstrated a significantly higher activity of both PI3K and Akt/PKB in IGF-1-stimulated SV SMCs than in IMA. We also observed an upregulation of IGF-1 receptors in the SV SMCs in response to IGF-1 stimulation with no effect in IMA SMCs. Our results demonstrate a differential activity of IGF-1-induced PI3K-Akt/PKB activation, which was quantitatively and temporally greater in the SV SMCs than in the IMA. This, at least in part, could explain the greater propensity of the SV conduits than the IMA to undergo intimal hyperplasia following CABG.