Canadian Journal of Cardiology

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

Published:December 29, 2014DOI:



      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.


      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.


      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.


      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.



      Les microARN (miARN) jouent un rôle dans le remodelage cardiaque, puis l’infarctus du myocarde aigu (IMA) peut réguler l’expression des miARN. Les miARN-208a (miR-208a) sont essentiels à l’expression des gènes impliqués dans l’hypertrophie et la fibrose du cœur. Les miR-208a activent l’expression de l’endogline et peuvent entraîner la fibrose cardiaque. On ne connaît pas le rôle des miR-208a et de l’endogline dans l’IMA. Nous avions pour objet d’examiner la régulation des miR-208a et de l’endogline dans l’IMA.


      La ligature de la partie proximale de l’artère interventriculaire antérieure était réalisée chez des rats adultes Sprague-Dawley pour provoquer l’IMA. L’échocardiographie était utilisée pour mesurer la taille du cœur et la fonction du ventricule gauche. Le dosage quantitatif en temps réel des miARN en sonde TaqMan était utilisé pour quantifier les miR-208a. La fibrose myocardique était détectée par coloration au trichrome de Masson.


      L’IMA et la surexpression des miR-208a dans le groupe recevant le traitement fictif sans infarctus a montré une augmentation significative de l’expression myocardique des miR-208a, de l’endogline et de la chaîne lourde de la β-myosine (β-MHC : β-myosin heavy chain). La surexpression de l’antagomir-208a inhibait significativement l’augmentation de l’expression myocardique de l’endogline et de la protéine β-MHC induite par l’infarctus. La surexpression des miR-208a mutants dans le groupe recevant le traitement fictif n’induisait pas l’expression myocardique de l’endogline et de la β-MHC. Le prétraitement par atorvastatine et par valsartan, un antagoniste des récepteurs de l’angiotensine, atténuait significativement l’augmentation de l’endogline et de la β-MHC induite par l’infarctus. L’IMA et la surexpression des miR-208a dans le groupe recevant le traitement fictif augmentaient significativement l’étendue de la fibrose myocardique comparativement au groupe recevant le traitement fictif. La surexpression de l’antagomir-208a et le prétraitement par atorvastatine et valsartan dans le groupe d’IMA diminuaient significativement l’étendue de la fibrose myocardique induite par l’infarctus.


      Les miR-208a augmentent l’expression de l’endogline pour induire la fibrose myocardique chez les rats souffrant d’IMA. Le traitement par atorvastatine et valsartan peut diminuer la fibrose myocardique induite par l’IMA en atténuant l’expression des miR-208a et de l’endogline.
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