ArticleCardiovascular research2020
Overexpression of p53 due to excess protein O-GlcNAcylation is associated with coronary microvascular disease in type 2 diabetes.
Article in Cardiovascular research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- Crosstalk between ubiquitination and other post-translational modifications in cardiovascular diseases.iScience · 2026Review
- CD22Science China. Life sciences · 2026Article
- Crosstalk between autophagy and ferroptosis in diabetes.Genes & diseases · 2026Review
- O-GlcNAcylation as a Metabolic Integrator in Cardiovascular Physiology and Disease.International journal of molecular sciences · 2026Review
- O-GlcNAcylation in diabetic cardiac remodeling and a proposed endothelial-macrophage-fibroblast network.Frontiers in immunology · 2026Review
- 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
- Glycosylation: mechanisms, biological functions and clinical implications.Signal transduction and targeted therapy · 2024Review
- Molecular Basis of Cardiomyopathies in Type 2 Diabetes.International journal of molecular sciences · 2024Review
- The Molecular Mechanisms of Cuproptosis and Small-Molecule Drug Design in Diabetes Mellitus.Molecules (Basel, Switzerland) · 2024Review
- Roles of O-GlcNAcylation in Mitochondrial Homeostasis and Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Prognostic value of myocardial flow reserve measured with CZT cardiac-dedicated SPECT low-dose dynamic myocardial perfusion imaging in patients with INOCA.Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2023Article
- Review
- The O-GlcNAc dichotomy: when does adaptation become pathological?Clinical science (London, England : 1979) · 2023Review
- Notch1 signaling activation alleviates coronary microvascular dysfunction through histone modification of Nrg-1 via the interaction between NICD and GCN5.Apoptosis : an international journal on programmed cell death · 2023Article
- Identification of 3-Phenylquinoline Derivative PQ1 as an Antagonist of p53 Transcriptional Activity.ACS omega · 2022Article
- Bladder Cancer-Derived Small Extracellular Vesicles Promote Tumor Angiogenesis by Inducing HBP-Related Metabolic Reprogramming and SerRS O-GlcNAcylation in Endothelial Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Mechanosensitive channel Piezo1 is required for pulmonary artery smooth muscle cell proliferation.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- The dual role of the hexosamine biosynthetic pathway in cardiac physiology and pathophysiology.Frontiers in endocrinology · 2022Review
- Efferocytosis of vascular cells in cardiovascular disease.Pharmacology & therapeutics · 2022Review
- Sodium-Glucose cotransporter 2 inhibitor empagliflozin decreases ventricular arrhythmia susceptibility by alleviating electrophysiological remodeling post-myocardial-infarction in mice.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsWe previously reported that increased protein O-GlcNAcylation in diabetic mice led to vascular rarefaction in the heart. In this study, we aimed to investigate whether and how coronary endothelial cell (EC) apoptosis is enhanced by protein O-GlcNAcylation and thus induces coronary microvascular disease (CMD) and subsequent cardiac dysfunction in diabetes. We hypothesize that excessive protein O-GlcNAcylation increases p53 that leads to CMD and reduced cardiac contractility. METHODS AND
resultsWe conducted in vivo functional experiments in control mice, TALLYHO/Jng (TH) mice, a polygenic type 2 diabetic (T2D) model, and EC-specific O-GlcNAcase (OGA, an enzyme that catalyzes the removal of O-GlcNAc from proteins)-overexpressing TH mice, as well as in vitro experiments in isolated ECs from these mice. TH mice exhibited a significant increase in coronary EC apoptosis and reduction of coronary flow velocity reserve (CFVR), an assessment of coronary microvascular function, in comparison to wild-type mice. The decreased CFVR, due at least partially to EC apoptosis, was associated with decreased cardiac contractility in TH mice. Western blot experiments showed that p53 protein level was significantly higher in coronary ECs from TH mice and T2D patients than in control ECs. High glucose treatment also increased p53 protein level in control ECs. Furthermore, overexpression of OGA decreased protein O-GlcNAcylation and down-regulated p53 in coronary ECs, and conferred a protective effect on cardiac function in TH mice. Inhibition of p53 with pifithrin-α attenuated coronary EC apoptosis and restored CFVR and cardiac contractility in TH mice.
conclusionsThe data from this study indicate that inhibition of p53 or down-regulation of p53 by OGA overexpression attenuates coronary EC apoptosis and improves CFVR and cardiac function in diabetes. Lowering coronary endothelial p53 levels via OGA overexpression could be a potential therapeutic approach for CMD in diabetes.
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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.