miR-431-5p Knockdown Protects Against Angiotensin II-Induced Hypertension and Vascular Injury
miR-431-5p Knockdown Protects Against Angiotensin II-Induced Hypertension and Vascular Injury
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DOI：
10.1161/hypertensionaha.119.12619
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发表时间：
2019-05-01
期刊：
影响因子：
8.3
通讯作者：
Schiffrin, Ernesto L.
中科院分区：
文献类型：
--
作者：
Huo, Ku-Geng;Richer, Chantal;Schiffrin, Ernesto L.
血管损伤是高血压的早期表现，也是终末器官损伤的原因之一。microrna在心血管疾病中发挥重要作用，但其在高血压血管损伤中的意义尚不清楚。本研究通过无偏方法、microRNA和mRNA测序及分子相互作用分析，揭示了一个microRNA-转录因子协同调节网络参与了14天输注Ang II（血管紧张素II）致高血压小鼠血管损伤。一种候选基因方法确定了保守的12qF1（人类14q32） microRNA簇中编码的上调miR-431-5p，其表达与血压相关，并且已被证明在人类动脉粥样硬化中上调，是Ang ii诱导的血管损伤的潜在关键调节因子。人血管平滑肌细胞的功能获得和功能丧失表明，miR-431-5p通过靶向ETS同源因子调控部分基因表达。体内miR-431-5p敲低延缓了Ang ii诱导的小鼠血压升高，减少了血管损伤，这证明了其作为治疗高血压和血管损伤的靶点的潜力。
Vascular injury is an early manifestation in hypertension and a cause of end-organ damage. MicroRNAs play an important role in cardiovascular disease, but their implication in vascular injury in hypertension remains unclear. This study revealed using an unbiased approach, microRNA and mRNA sequencing with molecular interaction analysis, a microRNA-transcription factor coregulatory network involved in vascular injury in mice made hypertensive by 14-day Ang II (angiotensin II) infusion. A candidate gene approach identified upregulated miR-431-5p encoded in the conserved 12qF1 (14q32 in humans) microRNA cluster, whose expression correlated with blood pressure, and which has been shown to be upregulated in human atherosclerosis, as a potential key regulator in Ang II-induced vascular injury. Gain-and loss-of-function in human vascular smooth muscle cells demonstrated that miR-431-5p regulates in part gene expression by targeting ETS homologous factor. In vivo miR-431-5p knockdown delayed Ang II-induced blood pressure elevation and reduced vascular injury in mice, which demonstrated its potential as a target for treatment of hypertension and vascular injury.