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

Shunsuke Yamada, Masatomo Taniguchi, Masanori Tokumoto, Jiro Toyonaga, Kiichiro Fujisaki, Takaichi Suehiro, Hideko Noguchi, Mitsuo Iida, Kazuhiko Tsuruya, Takanari Kitazono

Research output: Contribution to journalArticle

52 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)474-485
Number of pages12
JournalJournal of Bone and Mineral Research
Volume27
Issue number2
DOIs
Publication statusPublished - 2012

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Keywords

  • ANTIOXIDANT
  • ARTERIAL MEDIAL CALCIFICATION
  • CHRONIC KIDNEY DISEASE
  • OXIDATIVE STRESS
  • TEMPOL

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

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