Inhibition of microRNA-874 ameliorates cardiomyocyteapoptosis and improves cardiac function in theperipartum cardiomyopathy of Gαq transgenic mice

Abstract

 It is widely reported that microRNAs (miRNAs, miRs) play critical roles in the occurrence and development of peripartum cardiomyopathy (PPCM). Here, we aimed to explore the biological role of miR-874 and its underlying mechanisms in PPCM. To this purpose, a mouse model of PPCM was established through cardiacspecific overexpression of Gαq. Transthoracic echocardiography and left ventricular catheterization were used to examine the cardiac functions and hemodynamics. Apoptosis of the cardiomyocytes was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The direct interaction between miR-874 and signal transducer and activator of transcription 3 (STAT3) was confirmed by luciferase assay. The expression of apoptosis-related genes and proteins was evaluated by real-time quantitative reverse transcription polymerase chain reaction and Western blot, respectively. The results demonstrated that miR-874 inhibition significantly increased the survival and cardiac functions of pregnant Gαq transgenic mice. In addition, miR-874 inhibitor ameliorated cardiomyocyte apoptosis, downregulated both mRNA and protein levels of Bax, while upregulated those of Bcl-2. Further, STAT3 was found to be a direct target of miR-874. In addition, miR-874 inhibition increased the expression of STAT3 and janus kinase 2. In summary, miR-874 inhibition could improve cardiac functions and suppress cardiomyocyte apoptosis by targeting STAT3 during PPCM in Gαq transgenic mice.