2. Academic Validation
  3. N-acetylglucosaminyltransferase V attenuates myocardial infarction by mediating the insulin-like growth factor 1 receptor signaling pathway

N-acetylglucosaminyltransferase V attenuates myocardial infarction by mediating the insulin-like growth factor 1 receptor signaling pathway

  • J Transl Int Med. 2025 Jun 20;13(3):281-294. doi: 10.1515/jtim-2025-0021.
Tianqi Chang 1,  Yangya'nan Jin 2,  Chenyu Fan 1,  Hu Wang 1,  Ling Jin 1,  Yidan Shi 1,  Houhua Li 3,  Jiaxing Wang 1,  Ming Xu 1 4
Affiliations

Affiliations

  • 1 Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, China.
  • 2 College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
  • 3 State Key Laboratory of Natural and Biomimetic Drugs, Chemical Biology Center, School of Pharmaceutical Sciences, Peking University, Beijing, China.
  • 4 Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing, China.
PMID: 40896287 DOI: 10.1515/jtim-2025-0021
Abstract

Background and objectives: N-glycosylation, a crucial post-translational modification, is well-recognized for its pivotal role in cardiovascular functions. N-acetylglucosaminyltransferase V (GnT-V) is one of the major glycosyltransferases that determine the complexity of N-glycans in N-glycosylation modification. This study aimed to explore the role of GnT-V in myocardial infarction (MI).

Methods: Proteomics and N-glycoproteomic analysis were performed on myocardial tissues for the N-glycosylation profile after MI. Adeno-associated virus (AAV) with a mouse cTnT promoter was utilized to induce overexpression of GnT-V in the heart for the role of GnT-V in MI. Echocardiography and histological analysis were used to evaluate the effect of GnT-V on MI. For the potential mechanisms of GnT-V, proteomic analysis was performed on cardiomyocytes that were subjected to GnT-V overexpression and hypoxic stress. The results were validated by western blot, lectin blot and immunoprecipitation assays, and confirmed with PNGase F and tunicamycin treatment.

Results: N-glycosylation of protein was significantly reduced after MI, which could be related to a decrease in the expression levels of GnT-V and its target glycans. Targeted GnT-V overexpression in the heart by using AAV improved cardiac function and reduced the infarct size after MI. Further, proteomics analysis of cardiomyocytes revealed that insulin-like growth factor-binding protein 3 (IGFBP3) was targeted by GnT-V and induced degradation through the lysosome pathway. Consequently, the insulin-like growth factor 1 receptor (IGF1R) signaling pathway was activated through overexpression of GnT-V.

Conclusion: Our findings suggest that promoting the IGF1R signaling cascades by regulating the N-glycosylation of certain proteins in the signaling pathway, especially through GnT-V, may act as a promising strategy for treating MI.

Keywords

GnT-V; IGF1R; IGFBP3; N-glycosylation; myocardial infarction.

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