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29 May 2016 : Laboratory Research  

MicroRNA-208b Alleviates Post-Infarction Myocardial Fibrosis in a Rat Model by Inhibiting GATA4

Chaoyuan ZhouBCEF, Qintao CuiBCF, Guobao SuBDF, Xiaoliang GuoBF, Xiaochen LiuDF, Jie ZhangA

DOI: 10.12659/MSM.896428

Med Sci Monit 2016; 22:1808-1816


BACKGROUND: Myocardial infarction affects the health of many people. Post-infarction myocardial fibrosis has attracted much attention, but details of the mechanism remain elusive. In this study, the role of microRNA-208b (miR-208b) in modulating post-infarction myocardial fibrosis and the related mechanism were investigated.

MATERIAL AND METHODS: A rat model of myocardial infarction induced by ligating the left anterior descending artery was used to analyze the expression and roles of miR-208b by overexpression with the lentivirus vector of pre-miR-208b. Myocardial function was assessed and the expression of fibrosis-related factors type I collagen (COL1) and ACTA2 (alias αSMA) was detected. Myocardial fibroblasts isolated from newborn rats were transfected with luciferase reporter vectors containing wild-type or mutant Gata4 3’ UTR to verify the relationship between Gata4 and miR-208b. We then transfected the specific small interference RNA of Gata4 to detect changes in COL1 and ACTA2.

RESULTS: miR-208b was down-regulated in hearts of model rats (P<0.01). Overexpressing miR-208b improved myocardial functions, such as reducing the infarction area (P<0.05) and promoting LVEF and LVFS (P<0.01), and inhibited COL1 and ACTA2 (P<0.01). Luciferase reporter assay proved Gata4 to be the direct target of miR-208b, with the target sequence in the 3’UTR. Inhibiting GATA4 resulted in the down-regulation of COL1 and ACTA2, suggesting that the role of miR-208b was achieved via regulating GATA4.

CONCLUSIONS: This study demonstrates the protective function of miR-208b via GATA4 in post-infarction myocardial fibrosis, providing a potential therapeutic target for treating myocardial fibrosis.

Keywords: Actins - genetics, 3' Untranslated Regions, Collagen Type I - genetics, Endomyocardial Fibrosis - pathology, Fibroblasts - pathology, GATA4 Transcription Factor - metabolism, Myocardial Infarction - pathology



01 May 2022 : Editorial  

Editorial: Cardiovascular Complications at One Year After SARS-CoV-2 Infection are Independent of Underlying Cardiovascular Risk Factors or Severity of COVID-19

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.937048

Med Sci Monit 2022; 28:e937048


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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750