Chen Hanqing, Xu Xiru, Liu Zhengqing, Wu Yong
First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Endocrine, Suzhou Ninth People's Hospital, Suzhou, China.
J Vasc Res. 2021;58(3):180-190. doi: 10.1159/000514311. Epub 2021 Apr 1.
Hypertension is considered a risk factor for a series of systematic diseases. Known factors including genetic predisposition, age, and diet habits are strongly associated with the initiation of hypertension. The current study aimed to investigate the role of miR-22-3p in hypertension. In this study, we discovered that the miR-22-3p level was significantly decreased in the thoracic aortic vascular tissues and aortic smooth muscle cells (ASMCs) of spontaneously hypertensive rats. Functionally, the overexpression of miR-22-3p facilitated the switch of ASMCs from the synthetic to contractile phenotype. To investigate the underlying mechanism, we predicted 11 potential target mRNAs for miR-22-3p. After screening, chromodomain helicase DNA-binding 9 (CHD9) was validated to bind with miR-22-3p. Rescue assays showed that the co-overexpression of miR-22-3p and CHD9 reversed the inhibitory effect of miR-22-3p mimics on cell proliferation, migration, and oxidative stress in ASMCs. Finally, miR-22-3p suppressed vascular remodeling and oxidative stress in vivo. Overall, miR-22-3p regulated ASMC phenotype switch by targeting CHD9. This new discovery provides a potential insight into hypertension treatment.
高血压被认为是一系列系统性疾病的危险因素。已知的因素，包括遗传易感性、年龄和饮食习惯，与高血压的发病密切相关。本研究旨在探讨miR-22-3p在高血压中的作用。在本研究中，我们发现自发性高血压大鼠胸主动脉血管组织和主动脉平滑肌细胞（ASMCs）中miR-22-3p水平显著降低。在功能上，miR-22-3p的过表达促进了ASMCs从合成型向收缩型表型的转变。为了探究其潜在机制，我们预测了miR-22-3p的11个潜在靶mRNA。筛选后，验证了染色质结构域解旋酶DNA结合蛋白9（CHD9）与miR-22-3p结合。挽救实验表明，miR-22-3p和CHD9的共过表达逆转了miR-22-3p模拟物对ASMCs细胞增殖、迁移和氧化应激的抑制作用。最后，miR-22-3p在体内抑制血管重塑和氧化应激。总体而言，miR-22-3p通过靶向CHD9调节ASMC表型转换。这一新发现为高血压治疗提供了潜在的见解。
