Research on mechanism of miRNA-208a-3p overexpression leading to mitochondrial calcium overload and dysfunction in cardiomyocytes of chronic heart failure rats
Objective To explore the mechanism of miRNA-208a-3p promoting the occurrence and develop-ment of chronic heart failure by regulating mitochondrial calcium homeostasis and mitochondrial function.Methods 35 healthy SD rats were randomly divided into model group(n=20)and control group(n=15).The abdominal aorta diameter constriction method was used to establish a chronic heart failure model in the model group,while the control group underwent sham surgery.The model was evaluated via cardiac function and histopathology.The measurement included mitochondrial miR-208a-3p expression,mito-chondrial sirtuin 3(SIRT3)expression and NADH dehydrogenase 1(ND1)expression,mitochondrial Ca2+level,cardiomyocyte ROS production.Results The expression level of miR-208a-3p in the rat heart failure model group was significantly higher than that in the control group(P＜0.05);The expression level of SIRT3 protein in the model group was significantly lower than the control group(P＜0.001),and there was an significant negative correlation between the level of miR-208a-3p and SIRT3 protein.The ex-pression level of ND1 protein in the model group was significantly lower than that of the control group(P＜0.05),and there was a significant positive correlation between the level of ND1 and SIRT3 protein.The mitochondrial Ca2+level of left ventricular cardiomyocytes in the model group was significantly higher than that in the control group(P＜0.05).The ROS generation of cardiomyocytes in the model group was sig-nificantly higher than that in the control group(P＜0.05).Conclusion Over-expression of miR-208a-3p in chronic heart failure myocardial tissue is associated with decreased SIRT3/ND1 activity,which inhibits mitochondrial respiratory chain activity.In addition,myocardial cells exhibit mitochondrial calcium over-load and increased ROS generation,further exacerbating mitochondrial respiratory dysfunction,which is an important mechanism of mitochondrial dysfunction in chronic heart failure.
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