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Cardiovasc Diabetol. 2021, May 7; 20 (1): 99. doi: 10.1186 / s12933-021-01286-7.
ABSTRACT
RATIONAL: Approximately 50% of patients with diabetes mellitus (DM) in hospital 2019 (COVID-19) developed myocardial damage. The mechanisms of direct SARS-CoV-2 cardiomyocyte infection include viral invasion via ACE2 spike glycoprotein binding. In DM patients, the influence of the glycation of ACE2 on cardiomyocyte invasion by SARS-CoV-2 can be of great importance.
OBJECTIVE: To evaluate the presence of SARS-CoV-2 in cardiomyocytes from cardiac autopsy of DM cases compared to non-DM; Investigation of the role of DM in the onset of SARS-COV-2 in cardiomyocytes.
METHODS AND RESULTS: We studied consecutive autopsy cases that died between April 30, 2020 and January 18, 2021 of COVID-19 from Italy. We examined SARS-CoV-2 in cardiomyocytes, the expression of ACE2 (total and glycosylated form) and transmembrane protease serine protease-2 (TMPRSS2) protein. To investigate the role of diabetes in cardiomyocyte changes independently of COVID-19, we examined ACE2, glycosylated ACE2, and TMPRSS2 proteins in cardiomyocytes from DM and non-DM explant 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 assess the effects on binding to SARS-CoV-2 spike protein. The authors included heart tissue from 97 autopsies. DM was diagnosed in 37 patients (38%). Forty-seven out of 97 autopsies (48%) had SARS-CoV-2 RNA in cardiomyocytes. Thirty of 37 DM autopsy cases (81%) and 17 of 60 non-DM autopsy cases (28%) had SARS-CoV-2 RNA in cardiomyocytes. The total expression of ACE2, glycated ACE2 and TMPRSS2 protein was higher in cardiomyocytes from autopsied and explanted DM hearts than in non-DM. In vitro exposure of monomeric hACE2 to 120 mM glucose for 12 days resulted in nonenzymatic glycation of four lysine residues in the neck domain that influenced protein oligomerization.
CONCLUSIONS: The upregulation of ACE2 expression (total and glycosylated form) in DM cardiomyocytes as well as nonenzymatic glycation could increase the susceptibility to COVID-19 infections in DM patients by favoring the cellular entry of SARS-CoV2.
PMID: 33962629 | DOI: 10.1186 / s12933-021-01286-7
