Protein O-GlcNAcylation in cardiovascular diseases

Acta Pharmacol Sin. 2023 Jan;44(1):8-18. doi: 10.1038/s41401-022-00934-2. Epub 2022 Jul 11.

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; cardiovascular disease; glycomics; glycosylation.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases* / metabolism
  • Heart
  • Humans
  • Mitochondria / metabolism
  • N-Acetylglucosaminyltransferases / genetics
  • N-Acetylglucosaminyltransferases / metabolism
  • Protein Processing, Post-Translational
  • beta-N-Acetylhexosaminidases / genetics
  • beta-N-Acetylhexosaminidases / metabolism

Substances

  • beta-N-Acetylhexosaminidases
  • N-Acetylglucosaminyltransferases