MiR-375-3p Promotes Cardiac Fibrosis by Regulating the Ferroptosis Mediated by GPX4

Overview

Journal Comput Intell Neurosci

Specialty Biology

Date 2022 May 2

PMID 35498204

Authors

Yu Zhuang

Dicheng Yang

Sheng Shi

Limin Wang

Min Yu

Xiangdong Meng

Yongliang Fan

Ren Zhou

Feng Wang

Affiliations

Soon will be listed here.

Abstract

Although coronary artery recanalization after myocardial infarction improves patient outcomes, inadequate ventricular remodeling following ischemia-reperfusion (IR) injury and secondary cardiac fibrosis (CF) are common and can lead to heart failure. MicroRNAs (miRNAs) play an important role in cardiovascular disorders. However, the underlying molecular mechanism of miRNAs in the occurrence and progression of CF has not been fully elucidated. Herein, through the construction of an I/R rat model and an angiotensin II-induced CF cell model, we evaluated the role of miR-375-3p in the progression of CF. In the I/R rat model and CF cell model, miR-375-3p promoted fibrosis by accelerating the ferroptosis of cardiomyocytes through mediating glutathione peroxidase 4 (GPX4). Furthermore, we treated the rats or cell model with miR-375-3p antagomir (or inhibitor) and ferroptosis inhibitor Ferrostatin-1 (Fer-1). The results showed that miR-375-3p antagomir (or inhibitor) and Fer-1 promoted the antioxidant capacity of cardiac fibroblasts, reduced GPX4-mediated ferroptosis process and alleviated I/R-induced CF. In conclusion, this study revealed that miR-375-3p directly targeted GPX4-an inhibitor of the ferroptosis pathway. Meanwhile, miR-375-3p can be a new potential biomarker for the prevention and treatment of CF.

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