Quercetin attenuates vascular calcification by inhibiting oxidative stress and mitochondrial fission

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• 作者：Lei Cui¹ ; ^{cuilei0731@126.com} ; Zhong Li ; Xueying Chang ; Guangting Cong ; Lirong Hao ; ^{haolirong2015@163.com}
• 关键词：CKD ; Chronic kidney disease ; VSMCs ; vascular smooth muscle cells ; MGP ; matrix Gla protein ; Drp1 ; dynamin-like protein 1 ; ROS ; reactive oxygen species ; OGD ; oxygen glucose deprivation ; Pi ; inorganic phosphate
• 刊名：Vascular Pharmacology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：88
• 期：Complete
• 页码：21-29
• 全文大小：1499 K
• 卷排序：88

文摘

Vascular calcification is a strong independent predictor of increased cardiovascular morbidity and mortality and has a high prevalence among patients with chronic kidney disease. The present study investigated the effects of quercetin on vascular calcification caused by oxidative stress and abnormal mitochondrial dynamics both in vitro and in vivo. Calcifying vascular smooth muscle cells (VSMCs) treated with inorganic phosphate (Pi) exhibited mitochondrial dysfunction, as demonstrated by decreased mitochondrial potential and ATP production. Disruption of mitochondrial structural integrity was also observed in a rat model of adenine-induced aortic calcification. Increased production of reactive oxygen species, enhanced expression and phosphorylation of Drp1, and excessive mitochondrial fragmentation were also observed in Pi-treated VSMCs. These effects were accompanied by mitochondria-dependent apoptotic events, including release of cytochrome c from the mitochondria into the cytosol and subsequent activation of caspase-3. Quercetin was shown to block Pi-induced apoptosis and calcification of VSMCs by inhibiting oxidative stress and decreasing mitochondrial fission by inhibiting the expression and phosphorylation of Drp1. Quercetin also significantly ameliorated adenine-induced aortic calcification in rats. In summary, our findings suggest that quercetin attenuates calcification by reducing apoptosis of VSMCs by blocking oxidative stress and inhibiting mitochondrial fission.