Aluminum accumulation induced the calcification of vascular smooth muscle cells

• Main Authors: Hsun,Kuo-Hsun, 孫國訓
• Other Authors: Guo,Chih Hung
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/89016749930654128949

碩士 === 弘光科技大學 === 營養醫學研究所 === 101 === Abstract Recent studies have shown that patients undergoing hemodialysis and peritoneal dialysis have still higher circulating aluminum (Al) status than control subjects. Further, those patients show associations of Al concentration with increased oxidative damage and inflammation. There are evidence that oxidative stress, inflammatory cytokines, and hyperhomocysteinemia may contribute to the vascular calcification. Therefore, the effects of Al on vascular calcification need to be elucidated. The present investigation is aim to examine whether Al induce oxidative stress and inflammation and activate mitogen activated protein kinase (MAPK) signaling pathway, leading calcification in primary vascular smooth muscle cells (VSMCs). VSMCs were inoculated with different levels of Al (0, 27, 67.5, 135, and 1350 ng/ml) under 10 ng homocysteine/ml condition, and VSMCs were harvested after 4, 12, 24, 36, and 48 hours of treatment. Further, cell lysates and mitochondrial fractions were analyzed for Al and Ca concentrations, oxidative stress parameters, cytokines, mitochondrial membrane potential, along with activation of MAPK and osteopontin expression. Intracellular and mitochondrial concentrations of Al were increased directly responsive to Al treatment. Al was also suppressed the growth of VSMCs. Al treatments have decrease the activities of antioxidant enzyme glutathione peroxidase (GPx), and increased superoxide dismutase (SOD) and catalase. Also, Al-treated VSMCs showed significant increases in ROS together with tumor necrosis factor (TNF-a), transcriptional factor NF-B, and cyclooxygenase 2 expression. Impaired mitochondrial membrane potential, Ca accumulation, and overexpression of osteopontin were found in Al-treated VSMCs. In conclusion, intracellular and mitochondrial Al accumulation induces oxidant-antioxidant imbalance, high pro-inflammatory cytokines production, impairment of mitochondrial membrane potential, along with activation of MAPK and osteopontin expression, accelerating the calcification of VSMCs. Keywords：Aluminum, Vascular smooth muscle cells, Oxidative stress, Inflammation, Calcification.