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10.1186/s12933-021-01286-7

http://scihub22266oqcxt.onion/10.1186/s12933-021-01286-7
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33962629!8104461!33962629
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suck abstract from ncbi

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  • Glycated ACE2 receptor in diabetes: open door for SARS-COV-2 entry in cardiomyocyte #MMPMID33962629
  • D'Onofrio N; Scisciola L; Sardu C; Trotta MC; De Feo M; Maiello C; Mascolo P; De Micco F; Turriziani F; Municino E; Monetti P; Lombardi A; Napolitano MG; Marino FZ; Ronchi A; Grimaldi V; Hermenean A; Rizzo MR; Barbieri M; Franco R; Campobasso CP; Napoli C; Municino M; Paolisso G; Balestrieri ML; Marfella R
  • Cardiovasc Diabetol 2021[May]; 20 (1): 99 PMID33962629show ga
  • 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.
  • |Aged[MESH]
  • |Amino Acid Sequence[MESH]
  • |Angiotensin-Converting Enzyme 2/*biosynthesis[MESH]
  • |Autopsy[MESH]
  • |COVID-19/epidemiology/*metabolism/pathology[MESH]
  • |Cohort Studies[MESH]
  • |Diabetes Mellitus/*metabolism/pathology[MESH]
  • |Female[MESH]
  • |Humans[MESH]
  • |Italy/epidemiology[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Myocytes, Cardiac/*metabolism/pathology[MESH]
  • |Protein Binding/physiology[MESH]
  • |Protein Structure, Secondary[MESH]
  • |SARS-CoV-2/*metabolism[MESH]


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  • suck abstract from ncbi

    99 1.20 2021