The antioxidant tempol ameliorates arterial medial calcification in uremic rats: Important role of oxidative stress in the pathogenesis of vascular calcification in chronic kidney disease

氧化应激 发病机制 钙化 肾脏疾病 医学 抗氧化剂 内科学 疾病 内分泌学 病理 化学 生物化学
作者
Shunsuke Yamada,Masatomo Taniguchi,Masanori Tokumoto,Jiro Toyonaga,Kiichiro Fujisaki,Takaichi Suehiro,Hideko Noguchi,Mitsuo Iida,Kazuhiko Tsuruya,Takanari Kitazono
出处
期刊:Journal of Bone and Mineral Research [Wiley]
卷期号:27 (2): 474-485 被引量:107
标识
DOI:10.1002/jbmr.539
摘要

Abstract Vascular calcification is closely related to cardiovascular morbidity and mortality. Accumulating data indicate that oxidative stress is associated with dysfunction of various organs, including cardiovascular diseases in chronic kidney disease (CKD). However, it remains undetermined if oxidative stress induced by uremia promotes arterial medial calcification. The present study investigated the role of oxidative stress in the pathogenesis of arterial medial calcification in uremic rats. Rats with uremia induced by adenine-rich diet progressively developed arterial medial calcification, which was accompanied by time-dependent increases in both aortic and systemic oxidative stress. Immunohistochemical and biochemical analyses showed that the arterial medial calcification progressed in a time-dependent manner that is parallel to the osteogenic transdifferentiation of vascular smooth muscle cells. Accumulation of oxidative stress was also identified in the calcified regions. Time-course studies indicated that both oxidative stress and hyperphosphatemia correlated with arterial medial calcification. Tempol, an antioxidant, ameliorated osteogenic transdifferentiation of vascular smooth muscle cells and arterial medial calcification in uremic rats, together with reduction in aortic and systemic oxidative stress levels, without affecting serum biochemical parameters. Our data suggest that oxidative stress induced by uremia can play a role in the pathogenesis of vascular calcification in CKD, and that antioxidants such as tempol are potentially useful in preventing the progression of vascular calcification in CKD. © 2012 American Society for Bone and Mineral Research
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