ArticleJCI insight2021
HuR/Cx40 downregulation causes coronary microvascular dysfunction in type 2 diabetes.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Brown adipose tissue-derived exosomes ameliorate obesity-related hypertension via HuR-mediated restoration of endothelial function.International journal of obesity (2005) · 2026Article
- Connexin 40 in atrial fibrillation: pathophysiological roles and regulatory mechanisms.Annals of medicine · 2025Review
- The Double-Edged Effect of Connexins and Pannexins of Glial Cells in Central and Peripheral Nervous System After Nerve Injury.Molecular neurobiology · 2025Review
- Stem cell therapy: a promising frontier in modern medicine with a comprehensive overview of their biology and potential therapeutic applications in chronic non-healing cutaneous injuries.Inflammopharmacology · 2025Review
- mRNA metabolism regulator human antigen R (HuR) regulates age-related hearing loss in aged mice.Nature aging · 2025Article
- Enhanced lung endothelial glycolysis is implicated in the development of severe pulmonary hypertension in type 2 diabetes.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- RNA binding proteins (RBPs) on genetic stability and diseases.Global medical genetics · 2025Review
- Structural, biological, and biomedical implications of mRNA interactions with the master regulator HuR.NAR molecular medicine · 2025Review
- eNAMPT is a novel therapeutic target for mitigation of coronary microvascular disease in type 2 diabetes.Diabetologia · 2024Article
- Cx40 Suppresses Sprouting AngiogenesisBioelectricity · 2023Article
- Nox4 as a novel therapeutic target for diabetic vascular complications.Redox biology · 2023Review
- Small noncoding vault RNA2-1 disrupts gut epithelial barrier function via interaction with HuR.EMBO reports · 2023Article
- Advances in the study of RNA-binding proteins in diabetic complications.Molecular metabolism · 2022Review
- RNA-binding proteins in diabetic microangiopathy.Journal of clinical laboratory analysis · 2022Review
- Post-transcriptional control by RNA-binding proteins in diabetes and its related complications.Frontiers in physiology · 2022Review
- Restoration of coronary microvascular function by OGA overexpression in a high-fat diet with low-dose streptozotocin-induced type 2 diabetic mice.Diabetes & vascular disease researchArticle
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
Patients with diabetes with coronary microvascular disease (CMD) exhibit higher cardiac mortality than patients without CMD. However, the molecular mechanism by which diabetes promotes CMD is poorly understood. RNA-binding protein human antigen R (HuR) is a key regulator of mRNA stability and translation; therefore, we investigated the role of HuR in the development of CMD in mice with type 2 diabetes. Diabetic mice exhibited decreases in coronary flow velocity reserve (CFVR; a determinant of coronary microvascular function) and capillary density in the left ventricle. HuR levels in cardiac endothelial cells (CECs) were significantly lower in diabetic mice and patients with diabetes than the controls. Endothelial-specific HuR-KO mice also displayed significant reductions in CFVR and capillary density. By examining mRNA levels of 92 genes associated with endothelial function, we found that HuR, Cx40, and Nox4 levels were decreased in CECs from diabetic and HuR-KO mice compared with control mice. Cx40 expression and HuR binding to Cx40 mRNA were downregulated in CECs from diabetic mice. Cx40-KO mice exhibited decreased CFVR and capillary density, whereas endothelium-specific Cx40 overexpression increased capillary density and improved CFVR in diabetic mice. These data suggest that decreased HuR contributes to the development of CMD in diabetes through downregulation of gap junction protein Cx40 in CECs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.