Bolanle Israel O, Palmer Timothy M
Biomedical Institute for Multimorbidity, Centre for Biomedicine, Hull York Medical School, University of Hull, Hull HU6 7RX, UK.
Int J Mol Sci. 2025 Apr 2;26(7):3303. doi: 10.3390/ijms26073303.
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.
400多种不同类型的翻译后修饰（PTM），包括O-连接的N-乙酰葡糖胺化和磷酸化，共同协调蛋白质功能的几乎所有方面。通常，这些PTM会相互重叠，O-连接的N-乙酰葡糖胺化和磷酸化之间的具体关系备受关注。在过去十年中，这种动态相互作用的重要性已与几种心血管源性慢性疾病相关联。然而，对于这种相互作用在心血管疾病中血管平滑肌细胞功能障碍的病理生理意义知之甚少。O-连接的N-乙酰葡糖胺化发生在丝氨酸和苏氨酸残基上，而这些残基也是磷酸化的靶点。现在越来越多的研究表明，这些PTM之间高度调节的相互作用与血管完整性和稳态的改变有关。此外，大量证据表明，O-连接的N-乙酰葡糖胺化是内膜增生和血管再狭窄发病机制的重要因素，而内膜增生和血管再狭窄是导致长期静脉移植物失败的原因。在这篇综述中，我们评估了这种动态相互作用的重要性及其在心血管疾病中的作用，以及确定更有效治疗干预可能靶点的前景。
