{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:01:26Z","timestamp":1790085686762,"version":"4.0.1"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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\u2013small-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\u2013RAGE, 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.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1976141","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:14:00Z","timestamp":1790082840000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["O-GlcNAcylation in diabetic cardiac remodeling and a proposed endothelial-macrophage-fibroblast network"],"prefix":"10.3389","volume":"17","author":[{"given":"Jin","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Endocrinology, The 940th Hospital of Joint Logistic Support Force of Chinese People\u2019s Liberation Army","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The 940th Hospital of Joint Logistic Support Force of Chinese People\u2019s Liberation Army","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The 940th Hospital of Joint Logistic Support Force of Chinese People\u2019s Liberation Army","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, The 940th Hospital of Joint Logistic Support Force of Chinese People\u2019s Liberation Army","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Wei","sequence":"additional","affiliation":[{"name":"Lintao County People\u2019s Hospital","place":["Dingxi, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, The 940th Hospital of Joint Logistic Support Force of Chinese People\u2019s Liberation Army","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20240262","article-title":"The role of protein O-GlcNAcylation in diabetic cardiomyopathy","volume":"52","author":"Chatham","year":"2024","journal-title":"Biochem Soc Trans"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1542208","article-title":"The immunology of diabetic cardiomyopathy","volume":"16","author":"Song","year":"2025","journal-title":"Front Endocrinol 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