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

Autor: Andrea Ronchi, Francesco De Micco, Maria Consiglia Trotta, Vincenzo Grimaldi, Maria Rosaria Rizzo, Fabrizio Turriziani, Antonio Lombardi, Pasquale Monetti, Maria Napolitano, Michelangela Barbieri, Giuseppe Paolisso, Emilia Municinò, Celestino Sardu, Maria Luisa Balestrieri, Raffaele Marfella, Lucia Scisciola, Marisa De Feo, Ciro Maiello, Federica Zito Marino, Carlo Pietro Campobasso, Claudio Napoli, Nunzia D'Onofrio, Anca Hermenean, Renato Franco, Pasquale Mascolo, Maurizio Municinò
Přispěvatelé: D' Onofrio, N, Scisciola, L, Sardu, C, Trotta, Mc, De Feo, M, Maiello, C, Mascolo, P, De Micco, F, Turriziani, F, Municinò, E, Monetti, P, Lombardi, A, Napolitano, Mg, Zito Marino, F, Ronchi, A, Grimaldi, V, Hermenean, A, Rizzo, Mr, Barbieri, M, Franco, R, Campobasso, Cp, Napoli, C, Municinò, M, Paolisso, G, Balestrier, Ml, Marfella, R
Rok vydání: 2021
Předmět:
Male
medicine.medical_specialty
Endocrinology
Diabetes and Metabolism
ACE2
Cardiomyocyte
030204 cardiovascular system & hematology
Diabete
TMPRSS2
Protein Structure
Secondary
Cohort Studies
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Glycation
Diabetes mellitus
Internal medicine
Diabetes Mellitus
medicine
Humans
Diseases of the circulatory (Cardiovascular) system
Protein oligomerization
Myocytes
Cardiac
Amino Acid Sequence
Receptor
Original Investigation
Aged
030304 developmental biology
0303 health sciences
SARS-CoV-2
business.industry
Diabetes
COVID-19
Heart
Middle Aged
medicine.disease
In vitro
Endocrinology
Italy
RC666-701
Angiotensin-converting enzyme 2
Female
Angiotensin-Converting Enzyme 2
Autopsy
Cardiology and Cardiovascular Medicine
business
hormones
hormone substitutes
and hormone antagonists
Protein Binding
Zdroj: Cardiovascular Diabetology, Vol 20, Iss 1, Pp 1-16 (2021)
Cardiovascular Diabetology
ISSN: 1475-2840
DOI: 10.1186/s12933-021-01286-7
Popis: 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.
Databáze: OpenAIRE
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