Open AccessInhibition of Let‐7 micro RNA attenuates myocardial remodeling and improves cardiac function postinfarction in mice
Author(s) -
Tolonen AnnaMaria,
Magga Johanna,
Szabó Zoltán,
Viitala Pirkko,
Gao Erhe,
Moilanen AnneMari,
Ohukainen Pauli,
Vainio Laura,
Koch Walter J.,
Kerkelä Risto,
Ruskoaho Heikki,
Serpi Raisa
Publication year - 2014
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.56
Subject(s) - myocardial infarction , cardiac function curve , ejection fraction , ventricular remodeling , cardiac fibrosis , medicine , microrna , fibrosis , cardiology , heart failure , ligation , in vivo , reprogramming , biology , cell , gene , biochemistry , microbiology and biotechnology , genetics
The members of lethal‐7 (Let‐7) micro RNA (mi RNA ) 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 mi RNA 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 mi RNA was inhibited with a specific antagomir administered intravenously. The inhibition of Let‐7c mi RNA downregulated the levels of mature Let‐7c mi RNA 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 mi RNA may be beneficial for the prevention of postinfarction LV remodeling and progression of heart failure.