Key result
Swim training improves cardiac function and reduces fibrosis in post-MI mice by inhibiting fibroblast activation.
Why the study?
Postmenopausal women have higher risks of MI and cardiac dysfunction, but the molecular mechanisms underlying exercise-mediated cardiovascular protection in postmenopausal MI are not fully understood.
Swim training protects against post-MI cardiac dysfunction in ovariectomized mice by downregulating miR-21 and upregulating Sox7, thereby inhibiting cardiac fibroblast activation.
Swim training attenuated post-MI dysfunction in OVX mice; leaves open whether mechanisms translate to postmenopausal patients.
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 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 an miR-21 knockout mice model and an adeno-associated virus serotype 9 (AAV9)-mediated miR-21 overexpression mice 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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Hu et al. (2026) studied Postmenopausal myocardial infarction. Swim training / exercise vs. No exercise was evaluated on Cardiac systolic function, cardiomyocyte hypertrophy, myocardial fibrosis, and apoptosis. Swim training improved cardiac function and reduced fibrosis in ovariectomized mice post-MI by downregulating miR-21 and upregulating Sox7 to inhibit cardiac fibroblast activation.
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