title: 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.
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.
authors: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors: Shunsuke
authors: S
authors: Yamada
authors: Masatomo
authors: M
authors: Taniguchi
authors: Masanori
authors: M
authors: Tokumoto
authors: Jiro
authors: J
authors: Toyonaga
authors: Kiichiro
authors: K
authors: Fujisaki
authors: Takaichi
authors: T
authors: Suehiro
authors: Hideko
authors: H
authors: Noguchi
authors: Mitsuo
authors: M
authors: Iida
authors: Kazuhiko
authors: K
authors: Tsuruya
authors: Takanari
authors: T
authors: Kitazono
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001012:Aorta, Abdominal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D001158:Arteries / Q000187:drug effects / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002114:Calcinosis / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D054338:Cell Transdifferentiation / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D054559:Hyperphosphatemia / Q000097:blood / Q000150:complications / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications* / Q000473:pathology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology*; D014511:Uremia / Q000097:blood / Q000150:complications* / Q000473:pathology
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D003497:Cyclic N-Oxides; D013113:Spin Labels; D019255:NADPH Oxidases; C001803:tempol