title: MicroRNA-208a increases myocardial fibrosis via endoglin in volume overloading heart.
abstract: MicroRNA-208a (mir-208a) is essential for cardiac hypertrophy and fibrosis. Endoglin, a co-receptor of transforming growth factor-β is also essential for cardiac fibrosis. Endoglin has been shown to be a target of mir-208a in the in vitro mechanical stress model. Volume overload can lead to heart failure and cardiac fibrosis. The role of mir-208a and endoglin in volume overload heart failure is well known. We sought to investigate the mechanism of regulation of mir-208a and endoglin in volume overload-induced heart failure. Aorta-caval (AV) shunt was performed in adult Sprague-Dawley rats to induce volume overload. Heart weight and heart weight/body weight ratio significantly increased in AV shunt animals. AV shunt significantly increased left ventricular end-diastolic dimension as compared to sham group. Mir-208a was significantly induced by AV shunt from 3 to 14 days. Endoglin, myosin heavy chain-β and brain natriuretic peptide were significantly induced by AV shunt from 3 to 14 days. Overexpression of mir-208a in the sham group without AV shunt significantly increased endoglin expression similar to the AV shunt group. Antagomir-208a attenuated the endoglin expression induced by AV shunt. Pretreatment with atorvastatin also attenuated the endoglin expression induced by AV shunt. AV shunt significantly increased myocardial fibrosis as compared to sham group. Overexpression of mir-208a in the sham group significantly increased myocardial fibrosis. Antagomir-208a and atorvastatin significantly attenuated the myocardial fibrosis induced by AV shunt. In conclusion, mir-208a increased endoglin expression to induce myocardial fibrosis in volume overloaded heart failure. Treatment with atorvastatin can attenuate the myocardial fibrosis induced by volume overload through inhibition of endoglin expression.
authors.affiliation: School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan ; Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwa.
authors.forename: Bao-Wei
authors.initials: BW
authors.lastname: Wang
authors.affiliation: School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors.forename: Gong-Jhe
authors.initials: GJ
authors.lastname: Wu
authors.affiliation: Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwa.
authors.forename: Wen-Ping
authors.initials: WP
authors.lastname: Cheng
authors.affiliation: Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwa ; Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Kou-Gi
authors.initials: KG
authors.lastname: Shyu
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D004452:Echocardiography; D000071063:Endoglin; D005355:Fibrosis; D015870:Gene Expression; D005786:Gene Expression Regulation; D006439:Hemodynamics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D009929:Organ Size; D051381:Rats
chemical_list: D000071063:Endoglin; C501740:Eng protein, rat; D047908:Intracellular Signaling Peptides and Proteins; C569395:MIRN208 microRNA, rat; D035683:MicroRNAs