Key result
Loss of miR-132/212 did not significantly affect long-term cardiac function, adverse remodeling, or overall myocardial performance 4 weeks after permanent coronary occlusion in mice.
Why the study?
Although miR-132/212 was known to play a role in arteriogenesis and cardiac contractility regulation in mice, its role during ischemia in myocardial infarction was unexplored.
Absolute Event Rate: 18.8% vs 20.2%
p-value: p=>0.05
Despite baseline differences in contractility, the systemic loss of miR-132/212 does not confer long-term beneficial effects on cardiac function or remodeling after permanent coronary occlusion in mice.
Myocardial infarction (MI) is caused by occlusion of the coronary artery and induces ischemia in the myocardium and eventually a massive loss in cardiomyocytes. Studies have shown many factors or treatments that can affect the healing and remodeling of the heart upon infarction, leading to better cardiac performance and clinical outcome. Previously, miR-132/212 has been shown to play an important role in arteriogenesis in a mouse model of hindlimb ischemia and in the regulation of cardiac contractility in hypertrophic cardiomyopathy in mice. In this study, we explored the role of miR-132/212 during ischemia in a murine MI model. miR-132/212 knockout mice show enhanced cardiac contractile function at baseline compared to wild-type controls, as assessed by echocardiography. One day after induction of MI by permanent occlusion, miR-132/212 knockout mice display similar levels of cardiac damage as wild-type controls, as demonstrated by infarction size quantification and LDH release, although a trend towards more cardiomyocyte cell death was observed in the knockout mice as shown by TUNEL staining. Four weeks after MI, miR-132/212 knockout mice show no differences in terms of cardiac function, expression of cardiac stress markers, and fibrotic remodeling, although vascularization was reduced. In line with these in vivo observation, overexpression of miR-132 or miR-212 in neonatal rat cardiomyocyte suppresses hypoxia-induced cardiomyocyte cell death. Although we previously observed a role in the collateral formation and myocardial contractility, the absence of miR-132/212 did not affect the overall myocardial performance upon a permanent occlusion of the coronary artery. This suggests an interplay of different roles of this miR-132/212 before and during MI, including an inhibitory effect on cell death and angiogenesis, and a positive effect on cardiac contractility and autophagic response. Thus, spatial or tissue specific manipulation of this microRNA family may be essential to fully understand the roles and to develop interventions to reduce infarct size. .
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Lei et al. (2020) studied Myocardial Infarction. miR-132/212 knockout vs. Wild-type mice was evaluated on Left ventricular ejection fraction (LVEF) at 4 weeks post-MI (p=>0.05). Loss of miR-132/212 did not significantly affect long-term cardiac function, adverse remodeling, or overall myocardial performance 4 weeks after permanent coronary occlusion in mice.
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