miR-214 Attenuates Aortic Valve Calcification by Regulating Osteogenic Differentiation of Valvular Interstitial Cells.
miR-214 Attenuates Aortic Valve Calcification by Regulating Osteogenic Differentiation of Valvular Interstitial Cells.
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miR-214 通过调节瓣膜间质细胞的成骨分化减轻主动脉瓣钙化
DOI：
10.1016/j.omtn.2020.10.016
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发表时间：
2020-12-04
期刊：
影响因子：
--
通讯作者：
Xu Z
中科院分区：
文献类型：
--
作者：
Li N;Bai Y;Zhou G;Ma Y;Tan M;Qiao F;Li X;Shen M;Song X;Zhao X;Liu X;Xu Z
钙化性主动脉瓣疾病（CAVD）是老年人群中常见的心脏瓣膜疾病，瓣膜间质细胞（VIC）的异常成骨分化在主动脉瓣异位骨化的发病机制中起着关键作用。 miR-214已被证实参与成骨过程。在这里，我们的目的是研究 miR-214 在 CAVD 进展中的作用和机制。 CAVD 主动脉瓣叶中 miR-214 表达显着下调，同时成骨标志物上调。 miR-214的过度表达抑制了VIC的成骨分化，而沉默miR-214的表达则促进了这一功能。 miR-214直接靶向ATF4和Sp7来调节VIC的成骨细胞分化，这一点通过双荧光素酶报告基因测定和救援实验得到证实。 miR-214 敲除大鼠表现出较高的平均跨瓣速度和梯度。与野生型组相比，miR-214敲除大鼠主动脉瓣叶中成骨标志物的表达上调。综上所述，我们的研究表明 miR-214 通过直接靶向 ATF4 和 Sp7 调节 VIC 的成骨分化来抑制主动脉瓣钙化，表明 miR-214 可能作为 CAVD 靶向治疗的重要候选者。主动脉瓣叶中的 miR-214 失衡是导致钙化性主动脉瓣疾病 (CAVD) 进展的原因。 miR-214的下调消除了其对Sp7和ATF4翻译的抑制作用，从而促进CAVD的发展。这些结果表明 miR-214 可能为治疗 CAVD 提供一条途径。
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. miR-214 imbalance in aortic valve leaflets is responsible for the progress of calcific aortic valve disease (CAVD). Downregulation of miR-214 eliminates its inhibitory effect on translation of Sp7 and ATF4, thereby promoting the development of CAVD. These results suggested that miR-214 might provide an avenue for treating CAVD.
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影响因子：
16.6
作者：
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4.6
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影响因子：
4.6
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