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.
Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
Kou-Gi
KG
Shyu
Department of Medical Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Bao-Wei
BW
Wang
Department of Medical Education and Research, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Wen-Pin
WP
Cheng
Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan. Electronic address: m006459@ms.skh.org.tw.
Huey-Ming
HM
Lo
D000818:Animals; D000069059:Atorvastatin; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000071063:Endoglin; D005355:Fibrosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation; D006439:Hemodynamics / Q000502:physiology; D006538:Heptanoic Acids / Q000494:pharmacology; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D032342:Muscle Cells / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction / Q000379:methods; D011758:Pyrroles / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D000068756:Valsartan; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology
D000071063:Endoglin; C501740:Eng protein, rat; D006538:Heptanoic Acids; D047908:Intracellular Signaling Peptides and Proteins; C569395:MIRN208 microRNA, rat; D035683:MicroRNAs; D011758:Pyrroles; D013777:Tetrazoles; D000068756:Valsartan; D000069059:Atorvastatin; D014633:Valine