Hdac9 inhibits medial artery calcification through down-regulation of Osterix

Pengcheng He, Hongjiao Yu, Lei Jiang, Ziying Chen, Siying Wang, Vicky E Macrae, Xiaodong Fu, Dongxing Zhu

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUNDS: Medial artery calcification (MAC) significantly contributes to the increased cardiovascular death in patients with chronic kidney disease (CKD). Previous genome-wide association studies have shown that various genetic variants of the histone deacetylase Hdac9 are associated with cardiovascular disease, but the role of Hdac9 in MAC under CKD conditions remains unclear.

METHODS: High phosphate-induced vascular smooth muscle cell (VSMC) calcification and MAC in mice administered with vitamin D3 (vD) were used in the present study. Alizarin red staining, calcium quantitative assay, qPCR, western blotting and histology were performed.

RESULTS: Hdac9 expression was significantly down-regulated during high phosphate-induced vascular smooth muscle cell (VSMC) calcification and MAC in mice administered with vitamin D3 (vD). Furthermore, high phosphate treatment inhibited phosphorylation of Akt, and pharmacological inhibition of Akt signaling reduced Hdac9 expression in cultured VSMCs. Knockdown of Hdac9 significantly enhanced calcium deposition in VSMCs. Conversely, adenovirus mediated-overexpression of Hdac9 inhibited high phosphate induced VSMC in vitro calcification. Our subsequent mechanistic studies revealed that the anti-calcific effect of Hdac9 was mediated through down-regulation of osteoblast-specific transcription factor Osterix.

CONCLUSION: These data suggest that Hdac9 is a novel inhibitor of MAC and may represent a potential therapeutic target for MAC in CKD patients.

Original languageEnglish
Pages (from-to)106775
JournalVascular pharmacology
Early online date21 Jul 2020
DOIs
Publication statusE-pub ahead of print - 21 Jul 2020

Fingerprint Dive into the research topics of 'Hdac9 inhibits medial artery calcification through down-regulation of Osterix'. Together they form a unique fingerprint.

Cite this