Smooth muscle-selective nuclear factor-κB inhibition reduces phosphate-induced arterial medial calcification in mice with chronic kidney disease

Tadashi Yoshida, Maho Yamashita, Chihiro Horimai, Matsuhiko Hayashi

研究成果: Article

6 引用 (Scopus)

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Background--Hyperphosphatemia is a major factor promoting the formation of arterial medial calcification in chronic kidney disease (CKD). However, arterial medial calcification begins to occur during the early stages of CKD, when hyperphosphatemia is not yet apparent. It is predicted that other factors also play a role. The aim of the present study was to determine the role of proinflammatory nuclear factor-jB (NF-κB) signaling in smooth muscle cells (SMCs) for phosphate-induced arterial medial calcification in CKD mice. Methods and Results--We first sought to establish a novel mouse model of CKD with arterial medial calcification. CKD was induced in DBA/2 mice by feeding them a low concentration of adenine, and these mice were fed a normal or high-phosphorus diet. Severe calcification was seen in CKD mice fed the high-phosphorus diet, while it was undetectable in CKD mice fed the normal phosphorus diet or control mice fed the high-phosphorus diet. Arterial medial calcification was accompanied by phenotypic switching of SMCs into osteogenic cells. Interestingly, NF-κB inhibitors, tempol and triptolide, both reduced arterial medial calcification in CKD mice fed the high-phosphorus diet. Moreover, formation of arterial medial calcification, as well as SMC phenotypic switching, was also markedly attenuated in transgenic mice, in which the NF-κB activity was inhibited selectively in SMCs. Mechanistic studies revealed that Krüppel-like factor 4 was involved in NF-κB-induced SMC phenotypic switching and calcification. Conclusions--Results of the present studies suggest that the NF-κB signaling in SMCs plays an important role in high phosphateinduced arterial medial calcification in CKD.

元の言語English
記事番号e007248
ジャーナルJournal of the American Heart Association
6
発行部数11
DOI
出版物ステータスPublished - 2017 11 1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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