ArticleCardiovascular diabetology2021
Glycated ACE2 receptor in diabetes: open door for SARS-COV-2 entry in cardiomyocyte.
Article in Cardiovascular diabetology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- Quantifying the Excess Risk of Adverse COVID-19 Outcomes in Unvaccinated Individuals With Diabetes Mellitus, Hypertension, Ischaemic Heart Disease or Myocardial Injury: A Meta-Analysis.Frontiers in cardiovascular medicine · 2022Pooled it
- Comparison of the effect of intravenous dexamethasone and methylprednisolone on the treatment of hospitalized patients with COVID-19: a randomized clinical trial.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2022Trial
- Glycated ACE2 reduces anti-remodeling effects of renin-angiotensin system inhibition in human diabetic hearts.Cardiovascular diabetology · 2022Trial
- Trial
- Research progress on the association between viruses and cardiac diseases.Journal of virology · 2026Review
- Hyperglycemia-Induced Endothelial Dysfunction: From Classical Pathogenetic Mechanisms to Emerging Insights into ACE2 Protective Action.International journal of molecular sciences · 2026Review
- Unraveling the cardiovascular burden of long COVID: symptom profiles, underlying mechanisms, and clinical management insights.Frontiers in cardiovascular medicine · 2026Review
- Decoding long COVID-associated cardiovascular dysfunction: Mechanisms, models, and new approach methodologies.Journal of molecular and cellular cardiology · 2025Review
- Molecular dissection of the role of ACE2 in glucose homeostasis.Physiological reviews · 2025Review
- The Intersection of SARS-CoV-2 and Diabetes.Microorganisms · 2025Review
- Article
- Molecular analysis of long COVID and new-onset diabetes mellitus: pathobiological relationships and current mechanistic views.Frontiers in endocrinology · 2025Review
- Diabetic cardiomyopathy and COVID-19: intersecting pathways and amplified cardiovascular risk.Frontiers in pharmacology · 2025Review
- Risk impact of SARS-CoV-2 coronavirus and spike protein on cardiac tissue: a comprehensive review.Physiological research · 2024Review
- The Functions of SARS-CoV-2 Receptors in Diabetes-Related Severe COVID-19.International journal of molecular sciences · 2024Review
- Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells.Viruses · 2024Review
- BPP: a platform for automatic biochemical pathway prediction.Briefings in bioinformatics · 2024Article
- Effects of Two COVID-19 Lockdowns on HbA1c Levels in Patients with Type 1 Diabetes and Associations with Digital Treatment, Health Literacy, and Diabetes Self-Management: A Multicenter, Observational Cohort Study Over 3 Years.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2024Article
- Comparison of Cardiac Activated Fibroblast Imaging and Magnetic Resonance Imaging in Patients with COVID-19-Related Myocarditis.Reviews in cardiovascular medicine · 2024Article
- Diabetes Mellitus, Energy Metabolism, and COVID-19.Endocrine reviews · 2024Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleAbout 50% of hospitalized coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM) developed myocardial damage. The mechanisms of direct SARS-CoV-2 cardiomyocyte infection include viral invasion via ACE2-Spike glycoprotein-binding. In DM patients, the impact of glycation of ACE2 on cardiomyocyte invasion by SARS-CoV-2 can be of high importance.
objectiveTo evaluate the presence of SARS-CoV-2 in cardiomyocytes from heart autopsy of DM cases compared to Non-DM; to investigate the role of DM in SARS-COV-2 entry in cardiomyocytes. METHODS AND
resultsWe evaluated consecutive autopsy cases, deceased for COVID-19, from Italy between Apr 30, 2020 and Jan 18, 2021. We evaluated SARS-CoV-2 in cardiomyocytes, expression of ACE2 (total and glycosylated form), and transmembrane protease serine protease-2 (TMPRSS2) protein. In order to study the role of diabetes on cardiomyocyte alterations, independently of COVID-19, we investigated ACE2, glycosylated ACE2, and TMPRSS2 proteins in cardiomyocytes from DM and Non-DM explanted-hearts. Finally, to investigate the effects of DM on ACE2 protein modification, an in vitro glycation study of recombinant human ACE2 (hACE2) was performed to evaluate the effects on binding to SARS-CoV-2 Spike protein. The authors included cardiac tissue from 97 autopsies. DM was diagnosed in 37 patients (38%). Fourth-seven out of 97 autopsies (48%) had SARS-CoV-2 RNA in cardiomyocytes. Thirty out of 37 DM autopsy cases (81%) and 17 out of 60 Non-DM autopsy cases (28%) had SARS-CoV-2 RNA in cardiomyocytes. Total ACE2, glycosylated ACE2, and TMPRSS2 protein expressions were higher in cardiomyocytes from autopsied and explanted hearts of DM than Non-DM. In vitro exposure of monomeric hACE2 to 120 mM glucose for 12 days led to non-enzymatic glycation of four lysine residues in the neck domain affecting the protein oligomerization.
conclusionsThe upregulation of ACE2 expression (total and glycosylated forms) in DM cardiomyocytes, along with non-enzymatic glycation, could increase the susceptibility to COVID-19 infection in DM patients by favouring the cellular entry of SARS-CoV2.
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Registered trials
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