Glycated ACE2 receptor in diabetes : open door for SARS-COV-2 entry in cardiomyocyte
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
|---|---|
| Enthalten in: |
Cardiovascular diabetology - 20(2021), 1 vom: 07. Mai, Seite 99 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
D'Onofrio, Nunzia [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
ACE2 |
|---|
| Anmerkungen: |
Date Completed 19.05.2021 Date Revised 19.05.2021 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1186/s12933-021-01286-7 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM325143943 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM325143943 | ||
| 003 | DE-627 | ||
| 005 | 20231225191818.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s12933-021-01286-7 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1083.xml |
| 035 | |a (DE-627)NLM325143943 | ||
| 035 | |a (NLM)33962629 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a D'Onofrio, Nunzia |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Glycated ACE2 receptor in diabetes |b open door for SARS-COV-2 entry in cardiomyocyte |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 19.05.2021 | ||
| 500 | |a Date Revised 19.05.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ACE2 | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Cardiomyocyte | |
| 650 | 4 | |a Diabetes | |
| 650 | 4 | |a Heart | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 7 | |a ACE2 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 650 | 7 | |a Angiotensin-Converting Enzyme 2 |2 NLM | |
| 650 | 7 | |a EC 3.4.17.23 |2 NLM | |
| 700 | 1 | |a Scisciola, Lucia |e verfasserin |4 aut | |
| 700 | 1 | |a Sardu, Celestino |e verfasserin |4 aut | |
| 700 | 1 | |a Trotta, Maria Consiglia |e verfasserin |4 aut | |
| 700 | 1 | |a De Feo, Marisa |e verfasserin |4 aut | |
| 700 | 1 | |a Maiello, Ciro |e verfasserin |4 aut | |
| 700 | 1 | |a Mascolo, Pasquale |e verfasserin |4 aut | |
| 700 | 1 | |a De Micco, Francesco |e verfasserin |4 aut | |
| 700 | 1 | |a Turriziani, Fabrizio |e verfasserin |4 aut | |
| 700 | 1 | |a Municinò, Emilia |e verfasserin |4 aut | |
| 700 | 1 | |a Monetti, Pasquale |e verfasserin |4 aut | |
| 700 | 1 | |a Lombardi, Antonio |e verfasserin |4 aut | |
| 700 | 1 | |a Napolitano, Maria Gaetana |e verfasserin |4 aut | |
| 700 | 1 | |a Marino, Federica Zito |e verfasserin |4 aut | |
| 700 | 1 | |a Ronchi, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Grimaldi, Vincenzo |e verfasserin |4 aut | |
| 700 | 1 | |a Hermenean, Anca |e verfasserin |4 aut | |
| 700 | 1 | |a Rizzo, Maria Rosaria |e verfasserin |4 aut | |
| 700 | 1 | |a Barbieri, Michelangela |e verfasserin |4 aut | |
| 700 | 1 | |a Franco, Renato |e verfasserin |4 aut | |
| 700 | 1 | |a Campobasso, Carlo Pietro |e verfasserin |4 aut | |
| 700 | 1 | |a Napoli, Claudio |e verfasserin |4 aut | |
| 700 | 1 | |a Municinò, Maurizio |e verfasserin |4 aut | |
| 700 | 1 | |a Paolisso, Giuseppe |e verfasserin |4 aut | |
| 700 | 1 | |a Balestrieri, Maria Luisa |e verfasserin |4 aut | |
| 700 | 1 | |a Marfella, Raffaele |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cardiovascular diabetology |d 2002 |g 20(2021), 1 vom: 07. Mai, Seite 99 |w (DE-627)NLM119878380 |x 1475-2840 |7 nnns |
| 773 | 1 | 8 | |g volume:20 |g year:2021 |g number:1 |g day:07 |g month:05 |g pages:99 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1186/s12933-021-01286-7 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 20 |j 2021 |e 1 |b 07 |c 05 |h 99 | ||