Exercise-Induced miR-210 Promotes Cardiomyocyte Proliferation and Survival and Mediates Exercise-Induced Cardiac Protection against Ischemia/Reperfusion Injury

被引：14

作者：

Bei, Yihua ^{[1
,2
,3
,4
]}

Wang, Hongyun ^{[1
,2
,3
,4
]}

Liu, Yang ^{[5
]}

Su, Zhuhua ^{[1
,2
,3
,4
]}

Li, Xinpeng ^{[3
,4
,6
]}

Zhu, Yujiao ^{[1
,2
,3
,4
]}

Zhang, Ziyi ^{[1
,2
,3
,4
]}

Yin, Mingming ^{[1
,2
,3
]}

Chen, Chen ^{[1
,2
,3
]}

Li, Lin ^{[1
,2
,3
]}

Wei, Meng ^{[1
,2
,3
]}

Meng, Xiangmin ^{[1
,2
]}

Liang, Xuchun ^{[1
,2
,3
]}

Huang, Zhenzhen ^{[1
,2
,3
]}

Cao, Richard Yang ^{[7
]}

Wang, Lei ^{[8
]}

Li, Guoping ^{[9
,10
]}

Cretoiu, Dragos ^{[11
,12
]}

Xiao, Junjie ^{[1
,2
,3
,4
]}

机构：

[1] Shanghai Univ, Affiliated Nantong Hosp, Inst Geriatr, Peoples Hosp Nantong 6, Nantong 226011, Peoples R China

[2] Shanghai Univ, Sch Life Sci, Nantong 226011, Peoples R China

[3] Shanghai Univ, Joint Int Res Lab Biomat & Biotechnol Organ Repair, Minist Educ, Shanghai 200444, Peoples R China

[4] Shanghai Univ, Inst Cardiovasc Sci, Shanghai Engn Res Ctr Organ Repair, Sch Med,Cardiac Regenerat & Ageing Lab, Shanghai 200444, Peoples R China

[5] Tongji Univ, Shanghai Tongji Hosp, Dept Cardiol, Sch Med, Shanghai 200065, Peoples R China

[6] Shanghai Univ, Sch Environm & Chem Engn, Shanghai 200444, Peoples R China

[7] Fudan Univ, Shanghai Xuhui Cent Hosp, Zhongshan Xuhui Hosp, Shanghai Clin Res Ctr,Cardiac Rehabil Program, Shanghai 200031, Peoples R China

[8] Nanjing Univ Chinese Med, Dept Rehabil Med, Nanjing 210023, Peoples R China

[9] Massachusetts Gen Hosp, Cardiovasc Div, Boston, MA 02114 USA

[10] Harvard Med Sch, Boston, MA 02114 USA

[11] Carol Davila Univ Med & Pharm, Dept Med Genet, Bucharest 020031, Romania

[12] Alessandrescu Rusescu Natl Inst Mother & Child Hlt, Materno Fetal Assistance Excellence Unit, Bucharest 011062, Romania

来源：

RESEARCH | 2024年 / 7卷

关键词：

CURRENT KNOWLEDGE; REPERFUSION; DISEASE; GROWTH; IDENTIFICATION; MICRORNA-210; THERAPY; CDK10; CARDIOPROTECTION; ANGIOGENESIS;

D O I：

10.34133/research.0327

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Exercise can stimulate physiological cardiac growth and provide cardioprotection effect in ischemia/ reperfusion (I/R) injury. MiR-210 is regulated in the adaptation process induced by exercise; however, its impact on exercise -induced physiological cardiac growth and its contribution to exercise -driven cardioprotection remain unclear. We investigated the role and mechanism of miR-210 in exercise -induced physiological cardiac growth and explored whether miR-210 contributes to exercise -induced protection in alleviating I/R injury. Here, we first observed that regular swimming exercise can markedly increase miR210 levels in the heart and blood samples of rats and mice. Circulating miR-210 levels were also elevated after a programmed cardiac rehabilitation in patients that were diagnosed of coronary heart diseases. In 8 -week swimming model in wild -type (WT) and miR-210 knockout (KO) rats, we demonstrated that miR-210 was not integral for exercise -induced cardiac hypertrophy but it did influence cardiomyocyte proliferative activity. In neonatal rat cardiomyocytes, miR-210 promoted cell proliferation and suppressed apoptosis while not altering cell size. Additionally, miR-210 promoted cardiomyocyte proliferation and survival in human embryonic stem cell -derived cardiomyocytes (hESC-CMs) and AC16 cell line, indicating its functional roles in human cardiomyocytes. We further identified miR-210 target genes, cyclin-dependent kinase 10 (CDK10) and ephrin-A3 (EFNA3), that regulate cardiomyocyte proliferation and apoptosis. Finally, miR-210 KO and WT rats were subjected to swimming exercise followed by I/R injury. We demonstrated that miR-210 crucially contributed to exercise -driven cardioprotection against I/R injury. In summary, this study elucidates the role of miR-210, an exercise -responsive miRNA, in promoting the proliferative activity of cardiomyocytes during physiological cardiac growth. Furthermore, miR-210 plays an essential role in mediating the protective effects of exercise against cardiac I/R injury. Our findings suggest exercise as a potent nonpharmaceutical intervention for inducing miR-210, which can alleviate I/R injury and promote cardioprotection.

引用

页数：17

共 68 条

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