Inhibiting MicroRNA-497 Improves the Effects of Exercise Training on Myocardial Infarction

Abstract

Exercise training (ET) could improve myocardial infarction (MI), and microRNA-497 is highly associated with MI. This study aimed to investigate whether the regulation of miR-497 is involved in the positive effects of ET on MI. MI rat models induced by left anterior descending (LAD) were subjected to interval training and infarct size was observed. Blood and myocardial samples were collected from the rats for determining the expressions of miR-497. To evaluate the functions of miR-497, miR-497 agomir and antagomir were injected accordingly into grouped rats during ET, and subsequently, the expressions of apoptotic and inflammatory factors were determined. ET reduced the infarct size in MI rats and inhibited the levels of miR-497. MiR-497 agomir injection enlarged the infarct size, and reversed the shrunk infarct size induced by ET. However, miR-497 antagomir further promoted the positive effect on MI improved by ET. Chloride voltage-gated channel 3 (CLCN3) was identified as the most possible target for miR-497. Moreover, ET improving MI also involved the regulation of apoptotic and inflammatory factors. The mechanisms underlying the positive effects of ET on MI were highly associated with the regulation of miR-497.

Improvement of cardiac function by mesenchymal stem cells derived extracellular vesicles through targeting miR-497/Smad7 axis

“…Previous studies indicated that the level of cardiac troponin I, a biomarker of MI, was significantly positively correlated with the content of miR-497 in the serum [ 23 ]. Meanwhile, it was reported that exercise training could improve the cardiac function through suppressing the expression of miR-497 in the heart tissues after MI [ 24 ]. Our data suggested that overexpression of miR-497 could aggravate the cardiac function damage after MI, which is in line with previous study.…”

Exercise Training-Induced MicroRNA Alterations with Protective Effects in Cardiovascular Diseases

“…The expression of a set of cardiac miRNAs in response to exercise with cardio-protective roles to regulate cell proliferation, metabolism, and apoptosis has been reported [ 38 , 39 , 40 ] (Table 1 , Ref. [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ]). In response to physical exercise, these exercise-driven miRNAs have important roles in regulating exercise adaptation and could be used as promising therapeutic intervention.…”

“…ET could reduce miRNA-497-5p expression under physiological and under MI pathological conditions. A miRNA-497-5p antagomir (inhibitor) could mimic the benefits of exercise on MI, including reduced infarct size and improved cardiac function, whereas miRNA-497-5p agomir aggravated the infarct size post-MI and abrogated the positive effects of ET maybe through its target chloride voltage-gated channel 3 ( CLCN3 ) [ 47 ]. Through a plasma miRNA profiling assay, miR-1192 was found to be increased by a four-week swim training.…”