ATF3 affects myocardial fibrosis remodeling after myocardial infarction by regulating autophagy and its mechanism of action.

Yiwei Huang, Haiyue Dai

Gene 2023 Nov 15

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Myocardial fibrosis remodeling is a key event in the development of heart anomalousness and dysfunction after myocardial infarction (MI). The purpose of this study was to explore the effect of activating transcription factor 3 (ATF3) on myocardial fibrosis remodeling after MI and its underlying mechanism, so as to provide a theoretical basis for the clinical development of new strategies for MI treatment. MI mouse formers were structured by hypodesmus of the left anterior descending (LAD) arteria coronaria of mice, and primary cardiac fibroblasts (CFs) were separated and cultivated to investigate the effect of ATF3 on myocardial fibrosis after MI and its mechanism. Increased collagen content and autophagic flux were found in the left ventricle (LV) tissues of MI mice as shown by Sirius red staining and Western blotting (WB) analysis. Meanwhile, immunofluorescence staining and WB analysis showed that ATF3 was raised in response to MI damage. After remedy with angiotensin II (AngII), the activity and differentiation of CFs were significantly raised, the expression of collagens was increased, and the level of autophagy was notably increased. Furthermore, AngII stimulation remarkably raised the expression of ATF3. Interestingly, knockdown of ATF3 in AngII-CFs reversed the above changes. In addition, after intervention with 3-methyladenine (3-MA), an autophagy restrainer, the activity and differentiation of AngII-CFs, as well as the relative collagen levels and autophagic flux were reduced. However, up-regulation of ATF3 protein expression partially reversed the effect of 3-MA on AngII-CFs. ATF3 can regulate the proliferation of CFs and collagen production by affecting autophagy, thus affecting myocardial fibrosis remodeling after MI. Copyright © 2023 Elsevier B.V. All rights reserved.

Citation

Yiwei Huang, Haiyue Dai. ATF3 affects myocardial fibrosis remodeling after myocardial infarction by regulating autophagy and its mechanism of action. Gene. 2023 Nov 15;885:147705