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

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-& beta;1 resulted in a significant increase in miR-195-3p expression. Inhibition of miR-195-3p attenuated the TGF & beta;1-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-1953p markedly restored PTEN expression in MI mice and TGF-& beta;1-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.

Automated summary

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. This study found that inhibiting the expression of miR-195-3p can reduce myofibroblast differentiation and collagen deposition in cardiac fibroblasts, as well as protect cardiac function.