Expression of the SARS-CoV-2 receptorACE2 in human heart is associated with uncontrolled diabetes, obesity, and activation of the renin angiotensin system

Cardiovascular Diabetology

Ran Kornowski¹  Maayan Waldman²  Yaron Barak²  Amir Barnea²  Dan Aravot²  Edith Hochhauser³  Tali Guetta⁴  Michal Herman-Edelstein⁵  Naomi Ben-Dor⁵  Michael Arad⁶ 

[1] Cardiac Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine Tel-Aviv University, Tel Aviv, Israel;Department of Cardiology, Rabin Medical Center, 49100, Petach Tikva, Israel;Cardiac Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine Tel-Aviv University, Tel Aviv, Israel;Department of Cardiothoracic Surgery, Rabin Medical Center, Petach Tikva, Israel;Cardiac Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine Tel-Aviv University, Tel Aviv, Israel;Department of Cardiothoracic Surgery, Rabin Medical Center, Petach Tikva, Israel;Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;Cardiac Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine Tel-Aviv University, Tel Aviv, Israel;Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Tel Aviv University, Tel Aviv, Israel;Cardiac Research Laboratory, Felsenstein Medical Research Center, Sackler School of Medicine Tel-Aviv University, Tel Aviv, Israel;Nephrology Department, Rabin Medical Center, Petach Tikva, Israel;Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Tel Aviv University, Tel Aviv, Israel;

关键词: Corona virus 2 (SARS-CoV-2);    Angiotensin-converting enzyme 2 receptor (ACE2);    Heart;    Diabetes;    Renin–angiotensin system blockers;   

DOI  :  10.1186/s12933-021-01275-w

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY