CD44 N-Glycosylation Alleviates Myocardial Ischemia-Reperfusion Through PI3K/AKT/mTOR Pathway

Myocardial ischemia-reperfusion injury (MIRI) is one of the leading causes of morbidity and mortality from cardiovascular diseases worldwide. Protein N-glycosylation plays an important role in MIRI. However, there is limited knowledge regarding N-glycoproteins in MIRI and their alterations during MIRI. This study aims to investigate the dynamic changes of N-glycosylation modification in MIRI and the regulatory mechanisms of key proteins in MIRI to provide new therapeutic targets for the clinical diagnosis and treatment of MIRI. This study systematically explored the dynamic changes of N-glycosylation modification in MIRI through an integrated glycoproteomic analysis, combining a clinical sample, animal models, and cell models. Differential glycoproteins were identified using quantitative N-glycoproteomic mass spectrometry. Key regulatory molecules were screened through GO functional annotation and KEGG pathway enrichment. The integrated analysis identified 698 N-glycosylated proteins. Pathway enrichment analysis showed that the differentially expressed proteins were mainly involved in the PI3K/AKT/mTOR signaling pathway. The study of differentially expressed N-glycoproteins revealed that CD44 was upregulated and could regulate AKT. One possible reason is that N-glycosylation of CD44 affects its stability.