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MiR-214 Attenuates Aortic Valve Calcification by Regulating Osteogenic Differentiation of Valvular Interstitial Cells.


ABSTRACT: Calcific aortic valve disease (CAVD) is a common heart valve disease in aging populations, and aberrant osteogenic differentiation of valvular interstitial cells (VICs) plays a critical role in the pathogenesis of ectopic ossification of the aortic valve. miR-214 has been validated to be involved in the osteogenesis process. Here, we aim to investigate the role and mechanism of miR-214 in CAVD progression. miR-214 expression was significantly downregulated in CAVD aortic valve leaflets, accompanied by upregulation of osteogenic markers. Overexpression of miR-214 suppressed osteogenic differentiation of VICs, while silencing the expression of miR-214 promoted this function. miR-214 directly targeted ATF4 and Sp7 to modulate osteoblastic differentiation of VICs, which was proved by dual luciferase reporter assay and rescue experiment. miR-214 knockout rats exhibited higher mean transvalvular velocity and gradient. The expression of osteogenic markers in aortic valve leaflets of miR-214 knockout rats was upregulated compared to that of the wild-type group. Taken together, our study showed that miR-214 inhibited aortic valve calcification via regulating osteogenic differentiation of VICs by directly targeting ATF4 and Sp7, indicating that miR-214 may act as a profound candidate of targeting therapy for CAVD.

SUBMITTER: Li N 

PROVIDER: S-EPMC7679242 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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miR-214 Attenuates Aortic Valve Calcification by Regulating Osteogenic Differentiation of Valvular Interstitial Cells.

Li Ning N   Bai Yifan Y   Zhou Guangwei G   Ma Ye Y   Tan Mengwei M   Qiao Fan F   Li Xin X   Shen Ming M   Song Xiaowei X   Zhao Xianxian X   Liu Xiaohong X   Xu Zhiyun Z  

Molecular therapy. Nucleic acids 20201015


Calcific aortic valve disease (CAVD) is a common heart valve disease in aging populations, and aberrant osteogenic differentiation of valvular interstitial cells (VICs) plays a critical role in the pathogenesis of ectopic ossification of the aortic valve. miR-214 has been validated to be involved in the osteogenesis process. Here, we aim to investigate the role and mechanism of miR-214 in CAVD progression. miR-214 expression was significantly downregulated in CAVD aortic valve leaflets, accompan  ...[more]

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