MicroRNA-208a Increases Myocardial Endoglin Expression and Myocardial Fibrosis in Acute Myocardial Infarction.

BACKGROUND

MicroRNAs (miRs) play a role in cardiac remodelling, and acute myocardial infarction (AMI) can regulate miR expression. MiR-208a is essential for the expression of the genes involved in cardiac hypertrophy and fibrosis. MiR-208a activates endoglin expression and may result in cardiac fibrosis. The role of miR-208a and endoglin in AMI is not known. We sought to investigate the regulation of miR-208a and endoglin in AMI.

METHODS

Ligation of the proximal left anterior descending artery was performed in adult Sprague-Dawley rats to induce AMI. Echocardiography was used to measure heart size and left ventricular function. The TaqMan miR real-time quantitative assay was used to quantitate miR-208a. Myocardial fibrosis was detected by Masson trichrome staining.

RESULTS

AMI and overexpression of miR-208a in the sham group without infarction significantly increased myocardial miR-208a, endoglin, and β-myosin heavy chain (β-MHC) expression. Overexpression of antagomir-208a significantly inhibited the increase of myocardial endoglin and β-MHC protein expression induced by infarction. Overexpression of mutant miR-208a in the sham group did not induce myocardial endoglin and β-MHC expression. Pretreatment with atorvastatin and the angiotensin-receptor antagonist valsartan significantly attenuated the increase of endoglin and β-MHC induced by infarction. AMI and overexpression of miR-208a in the sham group significantly increased the area of myocardial fibrosis compared with the sham group. Overexpression of antagomir-208a and pretreatment with atorvastatin and valsartan in the AMI group significantly decreased the area of myocardial fibrosis induced by infarction.

CONCLUSIONS

MiR-208a increases endoglin expression to induce myocardial fibrosis in rats with AMI. Treatment with atorvastatin and valsartan can decrease myocardial fibrosis induced by AMI through attenuating miR-208a and endoglin expression.