Lack of Endothelial Nitric Oxide Synthase Accelerates Ectopic Calcification in Uremic Mice Fed an Adenine and High Phosphorus Diet

Yuji Oe, Shohei Mitsui, Emiko Sato, Naoko Shibata, Kiyomi Kisu, Akiyo Sekimoto, Mariko Miyazaki, Hiroshi Sato, Sadayoshi Ito, Nobuyuki Takahashi

研究成果: Article査読

抄録

Ectopic calcification is a risk of cardiovascular disease in chronic kidney disease (CKD) patients, and impaired endothelial nitric oxide synthase (eNOS) is involved in the CKD complications. However, whether eNOS dysfunction is a cause of ectopic calcification in CKD remains to be elucidated. To address this issue, we investigated the role of eNOS in ectopic calcification in mice with renal injury caused by an adenine and high-phosphorus (Ade + HP) diet. DBA/2J mice, a calcification-sensitive strain, were fed Ade + HP for 3 weeks. Expression levels of eNOS-related genes were reduced significantly in their calcified aorta. C57BL/6J is a calcification-resistant strain, and wild-type mice showed mild calcified lesions in the aorta and kidney when given an Ade + HP diet for 4 weeks. In contrast, a lack of eNOS led to the development of severe aortic calcification accompanied by an increase in runt-related transcription factor 2, an osteochondrogenic marker. Increased renal calcium deposition and the tubular injury score were remarkable in mice lacking eNOS-fed Ade + HP. Exacerbation of ectopic calcification by a lack of eNOS is associated with increased oxidative stress markers such as nicotinamide adenine dinucleotide phosphate oxidases. In conclusion, eNOS is critically important in preventing ectopic calcification. Therefore, the maintenance of eNOS is useful to reduce cardiovascular disease events and to improve prognosis in CKD patients.

本文言語English
ページ(範囲)283-293
ページ数11
ジャーナルAmerican Journal of Pathology
191
2
DOI
出版ステータスPublished - 2021 2

ASJC Scopus subject areas

  • 病理学および法医学

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