Authors
Jin Xu, Yan Li, Yan Zhang, Juan Feng, Yijun Wei, Fei Wang
Published in
Frontiers in immunology. Volume 17. Pages 1976141. Epub Sep 22, 2026.
Abstract
Diabetic cardiac remodeling involves microvascular dysfunction, inflammatory myeloid responses and fibroblast activation. O-linked beta-N-acetylglucosamine (O-GlcNAc) modification connects nutrient metabolism to protein function within each compartment, but its role in coordinating communication between them remains a hypothesis. This Mini Review evaluates that hypothesis against the available evidence. Diabetic models support causal effects of endothelial O-GlcNAc perturbation on coronary dysfunction, and an arterial endothelial CaMKIIalpha-small-extracellular-vesicle circuit provides evidence for persistent communication with cardiomyocytes after glucose normalization. Macrophage substrate mechanisms and fibroblast contractile responses are drawn partly from other organs or non-diabetic disease. Their relevance is therefore assessed separately from experimental design and human association. We compare O-GlcNAc with parallel AGE-RAGE, oxidative-stress and nutrient-sensing mechanisms, identify limitations of antibody-based and site-level measurements, and address sex as a biological variable. The synthesis supports O-GlcNAc as a candidate intracellular mediator of persistent multicellular remodeling, rather than an established intercellular coordinating signal. A consolidated experimental strategy tests whether endothelial O-GlcNAc is necessary for myeloid recruitment and subsequent fibrosis under matched glycemic conditions, and whether defined endothelial cargo rescues those effects. Cell-, substrate- and time-resolved interventions will be needed to separate pathogenic persistence from adaptive O-GlcNAc responses.
PMID:
42840636
Bibliographic data and abstract were imported from PubMed on 07 Oct 2026.
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