Exercise mitigates cardiac dysfunction post MI in ovariectomized mice via miR-21/Sox7-mediated suppression of cardiac fibroblast activation
5 affiliations
- 1Department of Cardiology, The Third Affiliated Hospital of Soochow University, The First People’s Hospital of Changzhou, Changzhou 213003, China
- 2Cardiac Rehabilitation Program, Shanghai Xuhui Central Hospital/Zhongshan-Xuhui Hospital, Fudan University/Shanghai Clinical Research Center, Shanghai 200031, China
- 3School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- 4Department of Rehabilitation Medicine, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
- 5Department of Cardiology, Geriatric Hospital of Jiangsu Province, Nanjing 210024, China
Abstract
Background: Postmenopausal women have higher risks of myocardial infarction (MI) and subsequent cardiac dysfunction. Exercise is widely recognized to protect the cardiovascular system, but its molecular mechanisms in postmenopausal MI are not fully understood. This study explored the effects and mechanisms of swim exercise against cardiac dysfunction in ovariectomized (OVX) mice post MI. Methods: OVX mice were subjected to a 3-week swim training before MI induction via permanent ligation of the left anterior descending artery. Cardiac systolic function was evaluated by echocardiography. Masson, hematoxylin-eosin (HE), wheat germ agglutinin (WGA) staining, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and western blotting were combined to detect the extent of cardiomyocyte hypertrophy, myocardial fibrosis, and apoptosis. To explore the key exercise-effectors, we detected microRNAs (miR-21, miR-146a, and miR-155) in serum samples of elderly post-MI women who performed exercise rehabilitation training. miR-21 expression was further investigated in heart samples of OVX plus MI mice. The role of miR-21 in vivo was elucidated through a miR-21 knockout mouse model and an adeno-associated virus serotype 9 (AAV9)-mediated miR-21 overexpression mouse model combined with ovariectomy treatment. The function of miR-21 in vitro was evaluated in cardiac fibroblasts isolated from OVX mice and treated with transforming growth factor-beta (TGF-β) to induce its activation. Target genes of miR-21 were identified by RNA-sequencing (RNA-seq) and validated using luciferase reporter assays and functional rescue experiments. Results: Swim training significantly improved cardiac function in OVX mice post MI, alleviated cardiomyocyte hypertrophy, reduced myocardial fibrosis, and inhibited apoptosis. miR-21 expression was downregulated by exercise training in the hearts of OVX mice post MI and in the serum of elderly women after MI. miR-21 knockout mice recapitulated the cardioprotective effects of swim training in OVX mice post MI, whereas miR-21 overexpression eliminated these effects. The overexpression of miR-21 promoted the TGF-β-induced differentiation of cardiac fibroblasts into myofibroblasts and their proliferation, whereas its inhibition blocked TGF-β’s pro-fibrotic role. RNA-seq and luciferase reporter assays identified SRY-box transcription factor 7 (Sox7) as a direct miR-21 target. Furthermore, Sox7 knockdown reversed anti-fibrotic effects conferred by miR-21 inhibition. Conclusion: Swim training protects against post-MI cardiac dysfunction in OVX mice by downregulating myocardial miR-21, thereby upregulating its target gene Sox7 and inhibiting cardiac fibroblast activation. miR-21 and its downstream target Sox7 contribute to the cardioprotective effects of swim training, offering a potential target for postmenopausal MI treatment.
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BibTeX
@article{hu2026exercise,
title = {{Exercise mitigates cardiac dysfunction post MI in ovariectomized mice via miR-21/Sox7-mediated suppression of cardiac fibroblast activation}},
author = {Meiyu Hu and Hui Wang and Yueyuan Mao and Junwen Tang and Tianxiang Yin and Ruoting Teng and Hao Yang and Qiqi Zhang and Wenqin Zhou and Shuyi Qiu and Richard Y. Cao and Dongchao Lu and Lei Wang and Peng Ji and Juan Gao and Junjie Xiao and Qiulian Zhou},
journal = {Journal of Sport and Health Science},
year = {2026},
month = oct,
doi = {10.1016/j.jshs.2026.101175},
url = {https://doi.org/10.1016/j.jshs.2026.101175},
note = {CC BY},
}
RIS
TY - JOUR
TI - Exercise mitigates cardiac dysfunction post MI in ovariectomized mice via miR-21/Sox7-mediated suppression of cardiac fibroblast activation
AU - Meiyu Hu
AU - Hui Wang
AU - Yueyuan Mao
AU - Junwen Tang
AU - Tianxiang Yin
AU - Ruoting Teng
AU - Hao Yang
AU - Qiqi Zhang
AU - Wenqin Zhou
AU - Shuyi Qiu
AU - Richard Y. Cao
AU - Dongchao Lu
AU - Lei Wang
AU - Peng Ji
AU - Juan Gao
AU - Junjie Xiao
AU - Qiulian Zhou
PY - 2026
DA - 2026/10/31
JO - Journal of Sport and Health Science
DO - 10.1016/j.jshs.2026.101175
UR - https://doi.org/10.1016/j.jshs.2026.101175
AB - Background: Postmenopausal women have higher risks of myocardial infarction (MI) and subsequent cardiac dysfunction. Exercise is widely recognized to protect the cardiovascular system, but its molecular mechanisms in postmenopausal MI are not fully understood. This study explored the effects and mechanisms of swim exercise against cardiac dysfunction in ovariectomized (OVX) mice post MI. Methods: OVX mice were subjected to a 3-week swim training before MI induction via permanent ligation of the left anterior descending artery. Cardiac systolic function was evaluated by echocardiography. Masson, hematoxylin-eosin (HE), wheat germ agglutinin (WGA) staining, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and western blotting were combined to detect the extent of cardiomyocyte hypertrophy, myocardial fibrosis, and apoptosis. To explore the key exercise-effectors, we detected microRNAs (miR-21, miR-146a, and miR-155) in serum samples of elderly post-MI women who performed exercise rehabilitation training. miR-21 expression was further investigated in heart samples of OVX plus MI mice. The role of miR-21 in vivo was elucidated through a miR-21 knockout mouse model and an adeno-associated virus serotype 9 (AAV9)-mediated miR-21 overexpression mouse model combined with ovariectomy treatment. The function of miR-21 in vitro was evaluated in cardiac fibroblasts isolated from OVX mice and treated with transforming growth factor-beta (TGF-β) to induce its activation. Target genes of miR-21 were identified by RNA-sequencing (RNA-seq) and validated using luciferase reporter assays and functional rescue experiments. Results: Swim training significantly improved cardiac function in OVX mice post MI, alleviated cardiomyocyte hypertrophy, reduced myocardial fibrosis, and inhibited apoptosis. miR-21 expression was downregulated by exercise training in the hearts of OVX mice post MI and in the serum of elderly women after MI. miR-21 knockout mice recapitulated the cardioprotective effects of swim training in OVX mice post MI, whereas miR-21 overexpression eliminated these effects. The overexpression of miR-21 promoted the TGF-β-induced differentiation of cardiac fibroblasts into myofibroblasts and their proliferation, whereas its inhibition blocked TGF-β’s pro-fibrotic role. RNA-seq and luciferase reporter assays identified SRY-box transcription factor 7 (Sox7) as a direct miR-21 target. Furthermore, Sox7 knockdown reversed anti-fibrotic effects conferred by miR-21 inhibition. Conclusion: Swim training protects against post-MI cardiac dysfunction in OVX mice by downregulating myocardial miR-21, thereby upregulating its target gene Sox7 and inhibiting cardiac fibroblast activation. miR-21 and its downstream target Sox7 contribute to the cardioprotective effects of swim training, offering a potential target for postmenopausal MI treatment.
SN - 2095-2546
ER -