Review Article

Protein O-GlcNAcylation in cardiovascular diseases

Hui-fang Wang1, Yi-xuan Wang1, Yu-ping Zhou2, Yun-peng Wei2, Yi Yan3,4, Ze-jian Zhang5, Zhi-cheng Jing2
1 Department of Medical Laboratory, Weifang Medical University, Weifang 261053, China
2 Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
3 Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University Munich, Munich, Germany
4 DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
5 Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Correspondence to: Ze-jian Zhang: zejianzhang2018@163.com, Zhi-cheng Jing: jingzhicheng@vip.163.com,
DOI: 10.1038/s41401-022-00934-2
Received: 7 February 2022
Accepted: 30 May 2022
Advance online: 11 July 2022

Abstract

O-GlcNAcylation is a post-translational modification of protein in response to genetic variations or environmental factors, which is controlled by two highly conserved enzymes, i.e. O-GlcNAc transferase (OGT) and protein O-GlcNAcase (OGA). Protein O-GlcNAcylation mainly occurs in the cytoplasm, nucleus, and mitochondrion, and it is ubiquitously implicated in the development of cardiovascular disease (CVD). Alterations of O-GlcNAcylation could cause massive metabolic imbalance and affect cardiovascular function, but the role of O-GlcNAcylation in CVD remains controversial. That is, acutely increased O-GlcNAcylation is an adaptive heart response, which temporarily protects cardiac function. While it is harmful to cardiomyocytes if O-GlcNAcylation levels remain high in chronic conditions or in the long run. The underlying mechanisms include regulation of transcription, energy metabolism, and other signal transduction reactions induced by O-GlcNAcylation. In this review, we will focus on the interactions between protein O-GlcNAcylation and CVD, and discuss the potential molecular mechanisms that may be able to pave a new avenue for the treatment of cardiovascular events.
Keywords: O-GlcNAcylation; glycomics; glycosylation; cardiovascular disease

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