-GlcNAcylation and Phosphorylation Crosstalk in Vascular Smooth Muscle Cells: Cellular and Therapeutic Significance in Cardiac and Vascular Pathologies.

More than 400 different types of post-translational modifications (PTMs), including -GlcNAcylation and phosphorylation, combine to co-ordinate almost all aspects of protein function. Often, these PTMs overlap and the specific relationship between -GlcNAcylation and phosphorylation has drawn much attention. In the last decade, the significance of this dynamic crosstalk has been linked to several chronic pathologies of cardiovascular origin. However, very little is known about the pathophysiological significance of this crosstalk for vascular smooth muscle cell dysfunction in cardiovascular disease. -GlcNAcylation occurs on serine and threonine residues which are also targets for phosphorylation. A growing body of research has now emerged linking altered vascular integrity and homeostasis with highly regulated crosstalk between these PTMs. Additionally, a significant body of evidence indicates that -GlcNAcylation is an important contributor to the pathogenesis of neointimal hyperplasia and vascular restenosis responsible for long-term vein graft failure. In this review, we evaluate the significance of this dynamic crosstalk and its role in cardiovascular pathologies, and the prospects of identifying possible targets for more effective therapeutic interventions.