tetano
Editor, Senior Moderator
Cardiovasc Diabetol
. 2021 May 7;20(1):99.
doi: 10.1186/s12933-021-01286-7.
Glycated ACE2 receptor in diabetes: open door for SARS-COV-2 entry in cardiomyocyte
Nunzia D'Onofrio[SUP] #[/SUP][SUP] 1 [/SUP], Lucia Scisciola[SUP] #[/SUP][SUP] 2 [/SUP], Celestino Sardu[SUP] 3 [/SUP], Maria Consiglia Trotta[SUP] 4 [/SUP], Marisa De Feo[SUP] 5 [/SUP], Ciro Maiello[SUP] 6 [/SUP], Pasquale Mascolo[SUP] 7 [/SUP], Francesco De Micco[SUP] 7 [/SUP], Fabrizio Turriziani[SUP] 2 [/SUP], Emilia Municin?[SUP] 8 [/SUP], Pasquale Monetti[SUP] 8 [/SUP], Antonio Lombardi[SUP] 8 [/SUP], Maria Gaetana Napolitano[SUP] 8 [/SUP], Federica Zito Marino[SUP] 9 [/SUP], Andrea Ronchi[SUP] 9 [/SUP], Vincenzo Grimaldi[SUP] 2 [/SUP], Anca Hermenean[SUP] 10 [/SUP], Maria Rosaria Rizzo[SUP] 2 [/SUP], Michelangela Barbieri[SUP] 2 [/SUP], Renato Franco[SUP] 9 [/SUP], Carlo Pietro Campobasso[SUP] 7 [/SUP], Claudio Napoli[SUP] 2 [/SUP], Maurizio Municin?[SUP] 8 [/SUP], Giuseppe Paolisso[SUP] 2 11 [/SUP], Maria Luisa Balestrieri[SUP] 1 [/SUP], Raffaele Marfella[SUP] 2 11 [/SUP]
Affiliations
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.
Keywords: ACE2; COVID-19; Cardiomyocyte; Diabetes; Heart; SARS-CoV-2.
. 2021 May 7;20(1):99.
doi: 10.1186/s12933-021-01286-7.
Glycated ACE2 receptor in diabetes: open door for SARS-COV-2 entry in cardiomyocyte
Nunzia D'Onofrio[SUP] #[/SUP][SUP] 1 [/SUP], Lucia Scisciola[SUP] #[/SUP][SUP] 2 [/SUP], Celestino Sardu[SUP] 3 [/SUP], Maria Consiglia Trotta[SUP] 4 [/SUP], Marisa De Feo[SUP] 5 [/SUP], Ciro Maiello[SUP] 6 [/SUP], Pasquale Mascolo[SUP] 7 [/SUP], Francesco De Micco[SUP] 7 [/SUP], Fabrizio Turriziani[SUP] 2 [/SUP], Emilia Municin?[SUP] 8 [/SUP], Pasquale Monetti[SUP] 8 [/SUP], Antonio Lombardi[SUP] 8 [/SUP], Maria Gaetana Napolitano[SUP] 8 [/SUP], Federica Zito Marino[SUP] 9 [/SUP], Andrea Ronchi[SUP] 9 [/SUP], Vincenzo Grimaldi[SUP] 2 [/SUP], Anca Hermenean[SUP] 10 [/SUP], Maria Rosaria Rizzo[SUP] 2 [/SUP], Michelangela Barbieri[SUP] 2 [/SUP], Renato Franco[SUP] 9 [/SUP], Carlo Pietro Campobasso[SUP] 7 [/SUP], Claudio Napoli[SUP] 2 [/SUP], Maurizio Municin?[SUP] 8 [/SUP], Giuseppe Paolisso[SUP] 2 11 [/SUP], Maria Luisa Balestrieri[SUP] 1 [/SUP], Raffaele Marfella[SUP] 2 11 [/SUP]
Affiliations
- PMID: 33962629
- DOI: 10.1186/s12933-021-01286-7
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.
Keywords: ACE2; COVID-19; Cardiomyocyte; Diabetes; Heart; SARS-CoV-2.