Proteomic analysis of homocysteine induced proliferation of cultured neonatal rat vascular smooth muscle cells

Abstract: Hyperhomocysteinemia is a common independent risk factor for cardiovascular diseases. The promoting effect of homocysteine (Hcy) on vascular smooth muscle cell (VSMC) proliferation has been considered as one of the important pathological bases of atherosclerosis. However, the mechanism of VSMC proliferation induced by Hcy remains unclear. The present research used proteomic techniques to globally analyze the protein changes in proliferative VSMCs. After comparing the protein expression profiles of VSMCs between the Hcy-treated and non-treated groups, 11 protein spots were found altered markedly in proliferative VSMCs with expression of eight protein spots increased and three protein spots decreased. In the differentially expressed proteins, eight protein spots were identified successfully including glycolytic metabolism proteins: pyruvate kinase M2 (PKM2), triosephosphate isomerase (TPI) and aldose reductase (AR); cytoskeletal proteins: lamin C and vimentin; and three other proteins: calreticulin; similar to WDR1 protein and LIM and SH3 protein 1. The differentially expressed proteins were further validated by Western blot and confirmed by assay of enzymes'' activities and ATP content. These results may provide some clues for comprehensively understanding the mechanism of VSMC proliferation and pathogenesis of atherosclerosis induced by Hcy. [Copyright &y& Elsevier]