PRMT4 overexpression aggravates cardiac remodeling following myocardial infarction by promoting cardiomyocyte apoptosis

Yilong Wang; Chenhui Ju; Ji Hu; Kai Huang; Ling Yang

doi:10.1016/j.bbrc.2019.10.085

PRMT4 overexpression aggravates cardiac remodeling following myocardial infarction by promoting cardiomyocyte apoptosis

Biochem Biophys Res Commun. 2019 Dec 10;520(3):645-650. doi: 10.1016/j.bbrc.2019.10.085. Epub 2019 Oct 16.

Authors

Yilong Wang¹, Chenhui Ju², Ji Hu³, Kai Huang⁴, Ling Yang⁵

Affiliations

¹ Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
³ Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: unionhuangkai@163.com.
⁵ Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: unionyangling@163.com.

PMID: 31627895
DOI: 10.1016/j.bbrc.2019.10.085

Abstract

Myocardial infarction due to coronary artery occlusion leads to adverse cardiac remodeling and heart failure. Apoptotic loss of cardiomyocytes near the ischemia area enlarges infarct area and promotes cardiac remodeling. Protein arginine methyltransferase 4 (PRMT4), a type I protein arginine methyltransferase, is involved in many cellular processes. Here we aimed to investigate the role of PRMT4 in cardiomyocyte apoptosis and myocardial infarction. We found that PRMT4 expression was markedly increased in ischemic heart and hypoxic cardiomyocytes. In vivo, cardiac-specific overexpression of PRMT4 in mice resulted in decreased survival rate, reduced left ventricular function, and aggravated cardiac remodeling following myocardial infarction. Mechanistically, PRMT4 overexpression promoted hypoxia-induced cardiomyocytes apoptosis, while its inhibition abolished these effects. Taken together, our work suggested an essential role of PRMT4 in myocardial infarction and cardiomyocyte apoptosis.

Keywords: Apoptosis; Myocardial infarction; PRMT4.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Apoptosis / genetics
Apoptosis / physiology
Cell Hypoxia / genetics
Cell Hypoxia / physiology
Cells, Cultured
Disease Models, Animal
Humans
Male
Mice
Mice, Inbred C57BL
Myocardial Infarction / enzymology*
Myocardial Infarction / genetics
Myocardial Infarction / pathology*
Myocardial Ischemia / enzymology
Myocardial Ischemia / genetics
Myocardial Ischemia / pathology
Myocytes, Cardiac / enzymology*
Myocytes, Cardiac / pathology*
Protein-Arginine N-Methyltransferases / antagonists & inhibitors
Protein-Arginine N-Methyltransferases / genetics
Protein-Arginine N-Methyltransferases / metabolism*
RNA, Small Interfering / genetics
Rats
Rats, Sprague-Dawley
Up-Regulation
Ventricular Remodeling / genetics
Ventricular Remodeling / physiology*

Substances

RNA, Small Interfering
Protein-Arginine N-Methyltransferases
coactivator-associated arginine methyltransferase 1