Vascular smooth muscle cell‐specific miRNA‐214 deficiency alleviates simulated microgravity‐induced vascular remodeling

Author:

Li Youyou12ORCID,Zhao Yunzhang23ORCID,Zhong Guohui24ORCID,Xu Qing5ORCID,Tan Yingjun2ORCID,Xing Wenjuan24ORCID,Cao Dengchao2ORCID,Wang Yinbo2ORCID,Liu Caizhi2ORCID,Li Jianwei2ORCID,Du Ruikai2ORCID,Sun Weijia2ORCID,Yuan Xinxin2ORCID,Li Yeheng2ORCID,Liu Zizhong2ORCID,Jin Xiaoyan2ORCID,Zhao Dingsheng2ORCID,Song Jinping2ORCID,Wang Yanqing2ORCID,Kan Guanghan2ORCID,Han Xuan2ORCID,Liu Shujuan2ORCID,Yuan Min2ORCID,Gao Feng4ORCID,Shu Jingdan1ORCID,Li Yingxian2ORCID,Ling Shukuan6ORCID

Affiliation:

1. Department of Physical Education China Agricultural University Beijing China

2. State Key Laboratory of Space Medicine Fundamentals and Application China Astronaut Research and Training Center Beijing China

3. Department of Cardiology & National Clinical Research Center for Geriatric Diseases Chinese PLA General Hospital Beijing China

4. School of Aerospace Medicine The Fourth Military Medical University Xi'an China

5. Core Facilities Center Capital Medical University Beijing China

6. Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health) Wenzhou China

Abstract

AbstractThe human cardiovascular system has evolved to accommodate the gravity of Earth. Microgravity during spaceflight has been shown to induce vascular remodeling, leading to a decline in vascular function. The underlying mechanisms are not yet fully understood. Our previous study demonstrated that miR‐214 plays a critical role in angiotensin II‐induced vascular remodeling by reducing the levels of Smad7 and increasing the phosphorylation of Smad3. However, its role in vascular remodeling evoked by microgravity is not yet known. This study aimed to determine the contribution of miR‐214 to the regulation of microgravity‐induced vascular remodeling. The results of our study revealed that miR‐214 expression was increased in the forebody arteries of both mice and monkeys after simulated microgravity treatment. In vitro, rotation‐simulated microgravity‐induced VSMC migration, hypertrophy, fibrosis, and inflammation were repressed by miR‐214 knockout (KO) in VSMCs. Additionally, miR‐214 KO increased the level of Smad7 and decreased the phosphorylation of Smad3, leading to a decrease in downstream gene expression. Furthermore, miR‐214 cKO protected against simulated microgravity induced the decline in aorta function and the increase in stiffness. Histological analysis showed that miR‐214 cKO inhibited the increases in vascular medial thickness that occurred after simulated microgravity treatment. Altogether, these results demonstrate that miR‐214 has potential as a therapeutic target for the treatment of vascular remodeling caused by simulated microgravity.

Publisher

Wiley

Subject

Genetics,Molecular Biology,Biochemistry,Biotechnology

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Omics Studies of Tumor Cells under Microgravity Conditions;International Journal of Molecular Sciences;2024-01-11

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