ArticleCardiovascular diabetology2021
Expression of the SARS-CoV-2 receptorACE2 in human heart is associated with uncontrolled diabetes, obesity, and activation of the renin angiotensin system.
Article in Cardiovascular diabetology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Angiotensin converting enzyme 2 level and its significance in COVID-19 and other diseases patients.European journal of clinical investigation · 2023Pooled it
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- Enalaprilat reverses neutrophil polarization imbalance via targeting taurine-STING axis for treatment of diabetic wounds.Cell reports. Medicine · 2026Article
- Clinical outcomes and predictive modeling in COVID-19 patients with type 2 diabetes mellitus: a multicenter retrospective cohort study.BMC infectious diseases · 2025Article
- SARS-CoV-2 spike protein-induced inflammation underlies proarrhythmia in COVID-19.Scientific reports · 2025Article
- Novel insights into the central protective role of ACE2 in diabetic cardiomyopathy: from underlying signaling pathways to therapeutic perspectives.Molecular and cellular biochemistry · 2025Review
- Nanomaterial-Based Biosensors for the Detection of COVID-19.Indian journal of microbiology · 2025Article
- The protective effect of serum antibodies in preventing SARS-CoV-2 virus entry into cardiac muscle.Physiological research · 2024Article
- ACE2 Knockout Mice Are Resistant to High-Fat Diet-Induced Obesity in an Age-Dependent Manner.International journal of molecular sciences · 2024Article
- Potential Effects of Hyperglycemia on SARS-CoV-2 Entry Mechanisms in Pancreatic Beta Cells.Viruses · 2024Review
- SARS-CoV-2 Spike Protein Enhances Carboxypeptidase Activity of Angiotensin-Converting Enzyme 2.International journal of molecular sciences · 2024Article
- New insights into the pathogenesis of SARS-CoV-2 during and after the COVID-19 pandemic.Frontiers in immunology · 2024Review
- Mechanisms influencing the high prevalence of COVID-19 in diabetics: A systematic review.Medical research archives · 2023Article
- Effect of dapagliflozin on COVID-19 infection and risk of hospitalization.The Journal of antimicrobial chemotherapy · 2023Article
- Diabetic cardiomyopathy: Early diagnostic biomarkers, pathogenetic mechanisms, and therapeutic interventions.Cell death discovery · 2023Review
- Cardiovascular Disease in Post-Acute COVID-19 Syndrome: A Comprehensive Review of Pathophysiology and Diagnosis Approach.Reviews in cardiovascular medicine · 2023Review
- The amplification of CNS damage in Alzheimer's disease due to SARS-CoV2 infection.Annals of diagnostic pathology · 2022Article
- Machine learning insights concerning inflammatory and liver-related risk comorbidities in non-communicable and viral diseases.World journal of gastroenterology · 2022Review
- Patients with allergic asthma have lower risk of severe COVID-19 outcomes than patients with nonallergic asthma.BMC pulmonary medicine · 2022Article
- Generation of Cytotoxic T Cells and Dysfunctional CD8 T Cells in Severe COVID-19 Patients.Cells · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiabetic and obese patients are at higher risk of severe disease and cardiac injury in corona virus 2 (SARS-CoV-2) infections. Cellular entry of SARS-CoV-2 is mainly via the angiotensin-converting enzyme 2 (ACE2) receptor, which is highly expressed in normal hearts. There is a disagreement regarding the effect of factors such as obesity and diabetes on ACE2 expression in the human heart and whether treatment with renin-angiotensin system inhibitors or anti-diabetic medications increases ACE2 expression and subsequently the susceptibility to infection. We designed this study to elucidate factors that control ACE2 expression in human serum, human heart biopsies, and mice.
methodsRight atrial appendage biopsies were collected from 79 patients that underwent coronary artery bypass graft (CABG) surgery. We investigated the alteration in ACE2 mRNA and protein expression in heart tissue and serum. ACE2 expression was compared with clinical risk factors: diabetes, obesity and different anti-hypertensive or anti-diabetic therapies. WT or db/db mice were infused with Angiotensin II (ATII), treated with different anti-diabetic drugs (Metformin, GLP1A and SGLT2i) were also tested.
resultsACE2 gene expression was increased in diabetic hearts compared to non-diabetic hearts and was positively correlated with glycosylated hemoglobin (HbA1c), body mass index (BMI), and activation of the renin angiotensin system (RAS), and negatively correlated with ejection fraction. ACE2 was not differentially expressed in patients who were on angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) prior to the operation. We found no correlation between plasma free ACE2 and cardiac tissue ACE2 expression. Transmembrane serine protease 2 (TMPRSS2), metalloprotease ADAM10 and ADAM17 that facilitate viral-ACE2 complex entry and degradation were increased in diabetic hearts. ACE2 expression in mice was increased with ATII infusion and attenuated following anti-diabetic drugs treatment.
conclusionPatients with uncontrolled diabetes or obesity with RAS activation have higher ACE2 expressions therefore are at higher risk for severe infection. Since ACEi or ARBs show no effect on ACE2 expression in the heart further support their safety.
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