Key result
Inhibition of Let-7c miRNA prevented the deterioration of cardiac function postinfarction in mice, demonstrated by preserved LV ejection fraction and elevated cardiac output.
Why the study?
Does Let-7c miRNA inhibition prevent postinfarction LV remodeling and improve cardiac function in mice?
Does Let-7c miRNA inhibition prevent postinfarction LV remodeling and improve cardiac function in mice?
Inhibition of Let-7c miRNA attenuates postinfarction LV remodeling and improves cardiac function in a mouse model, suggesting a potential therapeutic target for heart failure.
May attenuate post-MI remodeling in mice; leaves open translation to human HF therapy.
The members of lethal-7 (Let-7) microRNA (miRNA) family are involved in regulation of cell differentiation and reprogramming of somatic cells into induced pluripotent stem cells. However, their function in the heart is not known. In this study, we examined the effect of inhibiting the function of Let-7c miRNA on the progression of postinfarction left ventricular (LV) remodeling in mice. Myocardial infarction was induced with permanent ligation of left anterior descending coronary artery with a 4-week follow-up period. Let-7c miRNA was inhibited with a specific antagomir administered intravenously. The inhibition of Let-7c miRNA downregulated the levels of mature Let-7c miRNA and its other closely related members of Let-7 family in the heart and resulted in increased expression of pluripotency-associated genes Oct4 and Sox2 in cardiac fibroblasts in vitro and in adult mouse heart in vivo. Importantly, Let-7c inhibitor prevented the deterioration of cardiac function postinfarction, as demonstrated by preserved LV ejection fraction and elevated cardiac output. Improvement in cardiac function by Let-7c inhibitor postinfarction was associated with decreased apoptosis, reduced fibrosis, and reduction in the number of discoidin domain receptor 2-positive fibroblasts, while the number of c-kit(+) cardiac stem cells and Ki-67(+) proliferating cells remained unaltered. In conclusion, inhibition of Let-7 miRNA may be beneficial for the prevention of postinfarction LV remodeling and progression of heart failure.
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Tolonen et al. (2014) studied Myocardial infarction. Let-7c miRNA specific antagomir was evaluated on Progression of postinfarction left ventricular remodeling and cardiac function. Inhibition of Let-7c miRNA prevented the deterioration of cardiac function postinfarction in mice, demonstrated by preserved LV ejection fraction and elevated cardiac output.
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