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Article: Circulating ACE2 level and zinc/albumin ratio as potential biomarkers for a precision medicine approach to COVID-19
Title | Circulating ACE2 level and zinc/albumin ratio as potential biomarkers for a precision medicine approach to COVID-19 |
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Authors | |
Keywords | Albumin Diabetes Predictive markers Renin–angiotensin system Serum zinc Severe acute respiratory syndrome coronavirus-2 Zinc-chelation Zinc-metalloproteases |
Issue Date | 23-May-2023 |
Publisher | Elsevier |
Citation | Advances in Biological Regulation, 2023, v. 89 How to Cite? |
Abstract | Highly mutable influenza is successfully countered based on individual susceptibility and similar precision-like medicine approach should be effective against SARS-COV-2. Among predictive markers to bring precision medicine to COVID-19, circulating ACE2 has potential features being upregulated in both severe COVID-19 and predisposing comorbidities. Spike SARS-CoVs were shown to induce ADAM17-mediated shedding of enzymatic active ACE2, thus accounting for its increased activity that has also been suggested to induce positive feedback loops leading to COVID-19-like manifestations. For this reason, pre-existing ACE2 activity and inhibition of ACE2/ADAM17 zinc-metalloproteases through zinc chelating agents have been proposed to predict COVID-19 outcome before infection and to protect from COVID-19, respectively. Since most diagnostic laboratories are not equipped for enzymatic activity determination, other potential predictive markers of disease progression exploitable by diagnostic laboratories were explored. Concentrations of circulating albumin, zinc, ACE2 protein and its activity were investigated in healthy, diabetic (COVID-19-susceptible) and SARS-CoV-2-negative COVID-19 individuals. ACE2 both protein levels and activity significantly increased in COVID-19 and diabetic patients. Abnormal high levels of ACE2 characterised a subgroup (16–19%) of diabetics, while COVID-19 patients were characterised by significantly higher zinc/albumin ratios, pointing to a relative increase of albumin-unbound zinc species, such as free zinc ones. Data on circulating ACE2 levels are in line with the hypothesis that they can drive susceptibility to COVID-19 and elevated zinc/albumin ratios support the therapeutic use of zinc chelating inhibitors of ACE2/ADAM17 zinc-metalloproteases in a targeted therapy for COVID-19. |
Persistent Identifier | http://hdl.handle.net/10722/331543 |
ISSN | 2023 SCImago Journal Rankings: 1.114 |
DC Field | Value | Language |
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dc.contributor.author | Benedetti, S | - |
dc.contributor.author | Sisti, D | - |
dc.contributor.author | Vandini, D | - |
dc.contributor.author | Barocci, S | - |
dc.contributor.author | Sudano, M | - |
dc.contributor.author | Carlotti, E | - |
dc.contributor.author | Teng, JLL | - |
dc.contributor.author | Zamai, L | - |
dc.date.accessioned | 2023-09-21T06:56:47Z | - |
dc.date.available | 2023-09-21T06:56:47Z | - |
dc.date.issued | 2023-05-23 | - |
dc.identifier.citation | Advances in Biological Regulation, 2023, v. 89 | - |
dc.identifier.issn | 2212-4926 | - |
dc.identifier.uri | http://hdl.handle.net/10722/331543 | - |
dc.description.abstract | <p>Highly mutable influenza is successfully countered based on individual susceptibility and similar precision-like medicine approach should be effective against SARS-COV-2. Among predictive markers to bring precision medicine to COVID-19, circulating ACE2 has potential features being upregulated in both severe COVID-19 and predisposing comorbidities. Spike SARS-CoVs were shown to induce ADAM17-mediated shedding of enzymatic active ACE2, thus accounting for its increased activity that has also been suggested to induce positive feedback loops leading to COVID-19-like manifestations. For this reason, pre-existing ACE2 activity and inhibition of ACE2/ADAM17 zinc-metalloproteases through zinc chelating agents have been proposed to predict COVID-19 outcome before infection and to protect from COVID-19, respectively. Since most diagnostic laboratories are not equipped for <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/enzyme-activity" title="Learn more about enzymatic activity from ScienceDirect's AI-generated Topic Pages">enzymatic activity</a> determination, other potential predictive markers of disease progression exploitable by diagnostic laboratories were explored.</p><p>Concentrations of circulating albumin, zinc, ACE2 protein and its activity were investigated in healthy, diabetic (COVID-19-susceptible) and SARS-CoV-2-negative COVID-19 individuals.</p><p>ACE2 both protein levels and activity significantly increased in COVID-19 and diabetic patients. Abnormal high levels of ACE2 characterised a subgroup (16–19%) of diabetics, while COVID-19 patients were characterised by significantly higher zinc/albumin ratios, pointing to a relative increase of albumin-unbound zinc species, such as free zinc ones.</p><p>Data on circulating ACE2 levels are in line with the hypothesis that they can drive susceptibility to COVID-19 and elevated zinc/albumin ratios support the therapeutic use of zinc chelating inhibitors of ACE2/ADAM17 zinc-metalloproteases in a targeted therapy for COVID-19.</p> | - |
dc.language | eng | - |
dc.publisher | Elsevier | - |
dc.relation.ispartof | Advances in Biological Regulation | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Albumin | - |
dc.subject | Diabetes | - |
dc.subject | Predictive markers | - |
dc.subject | Renin–angiotensin system | - |
dc.subject | Serum zinc | - |
dc.subject | Severe acute respiratory syndrome coronavirus-2 | - |
dc.subject | Zinc-chelation | - |
dc.subject | Zinc-metalloproteases | - |
dc.title | Circulating ACE2 level and zinc/albumin ratio as potential biomarkers for a precision medicine approach to COVID-19 | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.jbior.2023.100973 | - |
dc.identifier.scopus | eid_2-s2.0-85162745571 | - |
dc.identifier.volume | 89 | - |
dc.identifier.eissn | 2212-4926 | - |
dc.identifier.issnl | 2212-4926 | - |