The effects of homocysteine- induced proliferation, free radicals, and calcification on vascular smooth muscle cells

• Main Authors: Tai Yi-Fen, 戴怡芬
• Other Authors: 陳伯中
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/91076140450225471646

碩士 === 弘光科技大學 === 營養醫學研究所 === 100 === Vascular calcification is highly correlated with cardiovascular mortality, especially in patients with end-stage renal disease (ESRD). Recently evidence suggests that high blood homocysteine (Hcy), increased oxidative stress, and hypercalcemia may contribute to vascular calcification. The average ranges of plasma Hcy in healthy subjects are 5-15 uM; whereas the plasma levels of Hcy are approximately 100~250 uM in hyperhomocysteinemia. Increased plasma Hcy levels are a well-known risk of elevated oxidative damage in vitro and in vivo. Thus, the pathobiomolecular mechanisms of Hcy-induced vascular calcification need to be explored. In the present thesis, we examined the effects of oxidative stress induction by Hcy on the calcification and proliferation of rat vascular smooth muscle cells (VSMCs). VSMCs treatment with different Hcy levels (10, 50, 100 and 250 M) had showed a dose-dependent significant increase in superoxide anion radical (O2-), hydrogen peroxide (H2O2), or lipid pro-oxidant production malondialdehyde (MDA). Increased antioxidant enzymes activities of superoxide dismutase (SOD) and catalase, as well as decreased glutathione peroxidase (GPx) were also observed in Hcy-treated VSMCs followed by increased incubation periods (24, 48, 72, and 96 hours). Further, Hcy treatment significantly promoted proliferation in the VSMCs by activated PI3K/p-Akt pathway. Also, VSMCs treatment with Hcy had showed a markedly elevation in intracellular calcium and are associated with active p-ERK protein expression. In summary, Hcy significantly induced an increase in intracellular calcium concentrations and proliferation may attribute to increased oxidative damage and activated PI3K/p-Akt pathway and p-ERK protein.