Revascularisation of type 2 diabetics with coronary artery disease: Insights and therapeutic targeting of O-GlcNAcylation

Bolanle, Israel O.; Riches-Suman, Kirsten; Loubani, Mahmoud; Williamson, Ritchie; Palmer, Timothy M.

Abstract

Background and Aim:
Coronary artery bypass graft (CABG) using autologous saphenous vein continues to be a gold standard procedure to restore the supply of oxygen-rich blood to the heart muscles in coronary artery disease (CAD) patients with or without type 2 diabetes mellitus (T2DM). However, CAD patients with T2DM are at higher risk of graft failure. While failure rates have been reduced through improvements in procedure-related factors, much less is known about the molecular and cellular mechanisms by which T2DM initiates vein graft failure. This review gives novel insights into these cellular and molecular mechanisms and identifies potential therapeutic targets for development of new medicines to improve vein graft patency.

Data Synthesis:
One important cellular process that has been implicated in the pathogenesis of T2DM is protein O-GlcNAcylation, a dynamic, reversible post-translational modification of serine and threonine residues on target proteins that is controlled by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Protein O-GlcNAcylation impacts a range of cellular processes, including trafficking, metabolism, inflammation and cytoskeletal organisation. Altered O-GlcNAcylation homeostasis have, therefore, been linked to a range of human pathologies with a metabolic component, including T2DM.

Conclusion:
We propose that protein O-GlcNAcylation alters vascular smooth muscle and endothelial cell function through modification of specific protein targets which contribute to the vascular re-modelling responsible for saphenous vein graft failure in T2DM.

Citation

Bolanle, I. O., Riches-Suman, K., Loubani, M., Williamson, R., & Palmer, T. M. (2021). Revascularisation of type 2 diabetics with coronary artery disease: Insights and therapeutic targeting of O-GlcNAcylation. Nutrition, metabolism, and cardiovascular diseases : NMCD, https://doi.org/10.1016/j.numecd.2021.01.017

• Journal Article Type: Review
• Acceptance Date: Jan 22, 2021
• Online Publication Date: Feb 1, 2021
• Publication Date: 2021-02
• Deposit Date: Feb 3, 2021
• Publicly Available Date: Feb 2, 2022
• Journal: Nutrition, Metabolism and Cardiovascular Diseases
• Print ISSN: 0939-4753
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1016/j.numecd.2021.01.017
• Keywords: Coronary artery disease; Coronary artery bypass graft; Type 2 diabetes mellitus; Protein O-GlcNAcylation
• Public URL: https://hull-repository.worktribe.com/output/3709929
• Publisher URL: https://www.nmcd-journal.com/article/S0939-4753(21)00037-5/pdf
• Related Public URLs: https://www.sciencedirect.com/science/article/abs/pii/S0939475321000375