NDLI: Glycated ACE2 receptor in diabetes: open door for SARS-COV-2 entry in cardiomyocyte

Content Provider	Springer Nature : BioMed Central
Author	D’Onofrio, Nunzia Scisciola, Lucia Sardu, Celestino Trotta, Maria Consiglia De Feo, Marisa Maiello, Ciro Mascolo, Pasquale De Micco, Francesco Turriziani, Fabrizio Municinò, Emilia Monetti, Pasquale Lombardi, Antonio Napolitano, Maria Gaetana Marino, Federica Zito Ronchi, Andrea Grimaldi, Vincenzo Hermenean, Anca Rizzo, Maria Rosaria Barbieri, Michelangela Franco, Renato Campobasso, Carlo Pietro Napoli, Claudio Municinò, Maurizio Paolisso, Giuseppe Balestrieri, Maria Luisa Marfella, Raffaele
Abstract	Rationale About 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. Objective To 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 results We 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. Conclusions The 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.
Related Links	https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-021-01286-7.pdf
Ending Page	16
Page Count	16
Starting Page	1
File Format	HTM / HTML
ISSN	14752840
DOI	10.1186/s12933-021-01286-7
Journal	Cardiovascular Diabetology
Issue Number	1
Volume Number	20
Language	English
Publisher	BioMed Central
Publisher Date	2021-05-07
Access Restriction	Open
Subject Keyword	Diabetes Angiology Cardiology COVID-19 SARS-CoV-2 Cardiomyocyte Heart ACE2
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Internal Medicine Endocrinology, Diabetes and Metabolism
Journal Impact Factor	8.5/2023
5-Year Journal Impact Factor	8.9/2023

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