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Updated: Dec 15, 2025
An Experimental Model of Myocardial Infarction for Studying Cardiac Repair and Remodeling in Knockout Mice
Published on: July 14, 2023
Knock-out of MicroRNA 145 impairs cardiac fibroblast function and wound healing post-myocardial infarction
Hui-Fang Song1,2,3, Sheng He2,3, Shu-Hong Li3
1Department of Anatomy, Shanxi Medical University, Taiyuan, China.
Abstract:
Prevention of infarct scar thinning and dilatation and stimulation of scar contracture can prevent progressive heart failure. Since microRNA 145 (miR-145) plays an important role in cardiac fibroblast response to wound healing and cardiac repair after an myocardial infarction (MI), using a miR-145 knock-out (KO) mouse model, we evaluated contribution of down-regulation of miR-145 to cardiac fibroblast and myofibroblast function during adverse cardiac remodelling. Cardiac function decreased more and the infarct size was larger in miR-145 KO than that in WT mice after MI and this phenomenon was accompanied by a decrease in cardiac fibroblast-to-myofibroblast differentiation. Quantification of collagen I and α-SMA protein levels as well as wound contraction revealed that transdifferentiation of cardiac fibroblasts into myofibroblasts was lower in KO than WT mice. In vitro restoration of miR-145 induced more differentiation of fibroblasts to myofibroblasts and this effect involved the target genes Klf4 and myocardin. MiR-145 contributes to infarct scar contraction in the heart and the absence of miR-145 contributes to dysfunction of cardiac fibroblast, resulting in greater infarct thinning and dilatation. Augmentation of miR-145 could be an attractive target to prevent adverse cardiac remodelling after MI by enhancing the phenotypic switch of cardiac fibroblasts to myofibroblasts.
Insights
MicroRNA 145 (miR-145) deficiency worsens heart attack outcomes by impairing cardiac fibroblast function and scar healing. Restoring miR-145 promotes scar contraction, offering a potential therapeutic target for heart failure.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Regenerative Medicine
Background:
- Progressive heart failure can result from infarct scar thinning and dilatation after myocardial infarction (MI).
- MicroRNA 145 (miR-145) is crucial for cardiac fibroblast function in wound healing and cardiac repair post-MI.
Purpose of the Study:
- To investigate the role of miR-145 down-regulation in cardiac fibroblast and myofibroblast function during adverse cardiac remodeling.
- To evaluate the impact of miR-145 deficiency on infarct scar characteristics and cardiac function post-MI.
Main Methods:
- Utilized a miR-145 knock-out (KO) mouse model and wild-type (WT) littermates subjected to MI.
- Assessed cardiac function, infarct size, fibroblast-to-myofibroblast differentiation, collagen I and α-SMA protein levels, and in vitro wound contraction.
- Investigated the effect of in vitro miR-145 restoration on fibroblast differentiation, involving target genes Klf4 and myocardin.
Main Results:
- miR-145 KO mice exhibited decreased cardiac function and larger infarct size compared to WT mice post-MI.
- Cardiac fibroblast-to-myofibroblast differentiation, collagen deposition, and scar contractility were reduced in miR-145 KO mice.
- In vitro restoration of miR-145 enhanced fibroblast differentiation into myofibroblasts, mediated by Klf4 and myocardin.
Conclusions:
- Absence of miR-145 leads to cardiac fibroblast dysfunction, promoting infarct thinning and dilatation, and contributing to adverse cardiac remodeling.
- MiR-145 is essential for infarct scar contraction and maintaining cardiac integrity post-MI.
- Augmenting miR-145 levels presents a promising therapeutic strategy to prevent adverse cardiac remodeling by enhancing fibroblast-to-myofibroblast differentiation.
