2009 Southern Regional Meeting Abstracts

Purpose of Study: The relevance of hyperhomocysteinemia (HHCY) as a risk factor for atherosclerosis is still unkown. In order to clarify the role of HHCY in the pathogenesis of atherosclerosis, the present study therefore investigated the effects of a pathophysiological concentration of homocysteine (HCY) (150 µM) on VSMC function in vitro.
Methods Used: Primary vascular smooth muscle cell (VSMC) were isolated from rat thoracic aortas and were grown in cultured medium-199. VSMC were treated for 24 h with pathophysiological levels of HCY (150 µM).
Summary of Results: Paradoxically, HCY increased both proliferation and apoptosis of VSMC and superoxide anions. Proteomic analysis showed that HCY upregulated several proteins including the beta-galactoside binding lectin, galectin-1. Strikingly, HCY increased the motility and migration of VSMC. Immunocytochemistry results indicted that galectin-1 expression is co-localized with apoptotic cells. Furthermore, upregulation of galectin-1 was associated with increased expression of nitrotyrosine and active caspase-3. Downregulation of galectin-1 by transfection of VSMC with galectin-1 specific small interfering RNA (siRNA) reduced HCY-induced VSMC apoptosis, superoxide anions production, VSMC proliferation and migration.
Conclusions: Our findings suggest that galectin-1 has pleotropic effects on VSMC and that it is an important mediator of many of the effects of HCY on VSMC. These findings provide insights into mechanisms whereby HCY promotes atherogenesis and provide a potential new therapeutic target for atherosclerotic vascular disease.