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作者

Junjie Pan, Jianwei Li, Jianhua Li, Shukuan Ling, Ruikai Du, Wenjuan Xing, Yuheng Li, Weijia Sun, Youyou Li, Yuanyuan Fan, Xinxin Yuan, Huiyuan Sun, Mingqi Yu, Xingyi Wang, Yingxian Li, Guohui Zhong

作者单位

Affiliations ¹ Suzhou Medical College of Soochow University, Suzhou, China. ² National Key Laboratory of Space Medicine, China Astronaut Research and Training Center, Beijing, China. ³ Department of Cardiology, The PLA Rocket Force Characteristic Medical Center, Beijing, China. ⁴ Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou Medical University, Wenzhou, China. ⁵ School of Aerospace Medicine, Key Laboratory of Aerospace Medicine of the Ministry of Education, Fourth Military Medical University, Xi'an, China. ⁶ School of Medical Technology, Beijing Institute of Technology, Beijing, China. ⁷ Department of Physical Education, China Agricultural University, Beijing, China. ⁸ The Third Affiliated Hospital of Beijing University of Traditional Chinese Medicine, Beijing, China. ⁹ Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Ji'nan, China.

刊名

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

年份

2025

卷号

Vol.39 No.2

页码

e70331

ISSN

1530-6860

关键词

MEF2C adeno‐associated virus cardiac miR‐199a‐3p remodeling simulated microgravity.

摘要

Microgravity-induced cardiac remodeling and dysfunction present significant challenges to long-term spaceflight, highlighting the urgent need to elucidate the underlying molecular mechanisms and develop precise countermeasures. Previous studies have outlined the important role of miRNAs in cardiovascular disease progression, with miR-199a-3p playing a crucial role in myocardial injury repair and the maintenance of cardiac function. However, the specific role and expression pattern of miR-199a-3p...更多

Microgravity-induced cardiac remodeling and dysfunction present significant challenges to long-term spaceflight, highlighting the urgent need to elucidate the underlying molecular mechanisms and develop precise countermeasures. Previous studies have outlined the important role of miRNAs in cardiovascular disease progression, with miR-199a-3p playing a crucial role in myocardial injury repair and the maintenance of cardiac function. However, the specific role and expression pattern of miR-199a-3p in microgravity-induced cardiac remodeling remain unclear. We separately utilized mouse tail suspension and rhesus monkey bedrest models to construct simulated microgravity conditions and observed significant cardiac remodeling and dysfunction in both species, accompanied by a marked downregulation of miR-199a-3p expression in their hearts. By generating cardiac-specific transgenic mice and subjecting them to tail suspension, we observed that the wild-type mice exhibited cardiac remodeling characterized by increased fibrosis, smaller cardiomyocytes, and reduced ejection fraction . In contrast, the miR-199a-3p TG mice were able to counteract the cardiac remodeling induced by tail suspension, demonstrating that miR-199a-3p can protect against simulated microgravity-induced cardiac remodeling. Subsequently, we employed an AAV9-mediated delivery system for cardiac-specific overexpression of miR-199a-3p, significantly mitigating cardiac remodeling and dysfunction induced by simulated microgravity. Mechanistically, miR-199a-3p targets MEF2C, inhibiting its activation induced by simulated microgravity, thereby suppressing the associated cardiac remodeling. This research identifies miR-199a-3p as a promising therapeutic target with significant potential for precise protection against spaceflight-induced cardiovascular dysfunction.收起

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