Inhibition of miR-195-3p protects against cardiac dysfunction and fibrosis after myocardial infarction

• Published in: International journal of cardiology Vol. 387; p. 131128
• Main Authors: Carvalho, Abdlay, Ji, Zhenjun, Zhang, Rui, Zuo, Wenjie, Qu, Yangyang, Chen, Xi, Tao, Zaixiao, Ji, Jingjing, Yao, Yuyu, Ma, Genshan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-09-2023
• Subjects: Cardiac fibrosis; miR-195-3p; Myocardial infarction; PTEN; PTEN/AKT signaling; Myocardial infarction; PTEN; Cardiac fibrosis; PTEN/AKT signaling; miR-195-3p
• DOI: 10.1016/j.ijcard.2023.131128
• EISSN: 1874-1754
• ISSN: 0167-5273

Cardiac fibrosis following myocardial infarction is a major risk factor for heart failure. Recent evidence suggests that miR-195-3p is up-regulated in fibrotic diseases, including kidney and liver fibrosis. However, its function and underlying mechanisms in cardiac fibrosis after MI remain unknown. To investigate the role of miR-195-3p in MI-induced cardiac fibrosis, we established acute MI models by ligating adult C57B/L6 mice LAD coronary artery while sham-operated mice were used as controls. In vivo inhibition of miR-195-3p was conducted by intramyocardial injection of AAV9-anti-miR-195-3p. In vitro overexpression and inhibition of miR-195-3p were performed by transfecting cultured Cardiac Fibroblasts (CFs) with synthetic miRNA mimic and inhibitor. Our results showed that MI induced the expression of miR-195-3p and that inhibition of miR-195-3p reduced myofibroblast differentiation and collagen deposition and protected cardiac function. In vitro stimulation of CFs with TGF-β1 resulted in a significant increase in miR-195-3p expression. Inhibition of miR-195-3p attenuated the TGF-β1-induced expression of ECM proteins, migration, and proliferation. PTEN expression was significantly reduced in the hearts of MI mice, in activated CFs, and in CFs transfected with miR-195-3p mimic. Inhibition of miR-195-3p markedly restored PTEN expression in MI mice and TGF-β1-treated CFs. In conclusion, this study highlights the crucial role of miR-195-3p in promoting cardiac fibrosis and dysfunction after MI. Inhibiting miR-195-3p could be a promising therapeutic strategy for preventing cardiac fibrosis and preserving cardiac function after MI. Additionally, the study sheds light on the mechanisms underlying the effects of miR-195-3p on fibrosis, including its regulation of PTEN/AKT pathway.
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•Inhibition of miR-195-3p reduces myofibroblast differentiation and collagen deposition and protects cardiac function after MI;•Overexpression of miR-195-3p in CFs promoted migration and proliferation in vitro;•Inhibition of miR-195-3p attenuates TGF-β1-induced expression of ECM proteins, and migration, and proliferation of CFs;•miR-195-3p targets PTEN expression in the hearts of MI mice and in activated CFs to promote fibrosis in vivo and in vitro;•Inhibition of miR-195-3p reduces migration and proliferation of activated CFs through regulation of PTEN/AKT signaling.