Key result
miR-146a inhibition improves LVEF and attenuates post-MI cardiac remodeling in preclinical heart failure.
Why the study?
The study was conducted to determine the roles of microRNA-146a in myocardial infarction-induced heart failure and cardiac remodeling.
Does inhibition of miR-146a improve cardiac dysfunction and attenuate remodeling in a rat model of myocardial infarction-induced heart failure?
Does inhibition of miR-146a improve cardiac dysfunction and attenuate remodeling in a rat model of myocardial infarction-induced heart failure?
p-value: p=<0.05
Inhibition of miR-146a improves left ventricular function and attenuates adverse cardiac remodeling in a rat model of myocardial infarction, suggesting a potential therapeutic target for heart failure.
Hypothesis-generating for miR-146a inhibition in post-MI heart failure; leaves open translation to human therapy.
The aim of the present study was to determine the roles of microRNA (miR)-146a on myocardial infarction (MI)-induced heart failure and cardiac remodeling. Experiments were carried out in Sprague-Dawley rats treated with ligation of left coronary artery to induce heart failure, and in primary neonatal rat cardiac fibroblasts (CFs) and cardiomyocytes treated with angiotensin (Ang) II. Four weeks after MI, rats were injected with miR-146a antagomiR or agomiR via tail vein. After 2 weeks of injection, the rats were killed. In MI rats, left ventricle (LV) ejection fraction and fractional shortening were reduced, and LV volumes in diastole and systole were increased, which were reversed by miR-146a antagomiR, and further exacerbated after miR-146a agomiR treatment. Administration of miR-146a antagomiR improved the decreases of LV ±dp/dtmax and LV systolic pressure (LVSP), and the increase in LV end-diastolic pressure (LVEDP) of MI rats, but miR-146a agomiR deteriorated the LV ±dp/dtmax, LVSP and LVEDP. The increases in the levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), collagen I and collagen III in the heart, and ST2 and norepinephrine in the serum of MI rats were inhibited by miR-146a antagomiR, but aggravated after miR-146a agomiR treatment. The increases of collagen I and collagen III levels induced by Ang II in CFs, and the increases of ANP and BNP levels induced by Ang II in cardiomyocytes were inhibited by miR-146a antagomiR, but aggravated by miR-146a agomiR. These results demonstrated that inhibition of miR-146a improved cardiac dysfunction and cardiac remodeling in heart failure rats.
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He et al. (2019) studied Myocardial infarction-induced heart failure and cardiac remodeling. miR-146a antagomiR vs. Sham or MI control was evaluated on Cardiac dysfunction and remodeling (echocardiography and hemodynamics) (p=<0.05). Inhibition of miR-146a with antagomiR significantly improved left ventricular ejection fraction, fractional shortening, cardiac hemodynamics, and attenuated cardiac remodeling in rats with myocardial infarction-induced heart failure.
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