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Article ; Online: ACE2 Elevation in Severe COVID-19.

Reindl-Schwaighofer, Roman / Hödlmoser, Sebastian / Eskandary, Farsad / Poglitsch, Marko / Bonderman, Diana / Strassl, Robert / Aberle, Judith H / Oberbauer, Rainer / Zoufaly, Alexander / Hecking, Manfred

American journal of respiratory and critical care medicine

2021 Volume 203, Issue 9, Page(s) 1191–1196

MeSH term(s)	Aged ; Biomarkers/blood ; COVID-19/blood ; COVID-19/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Peptidyl-Dipeptidase A/blood ; SARS-CoV-2 ; Severity of Illness Index
Chemical Substances	Biomarkers ; Peptidyl-Dipeptidase A (EC 3.4.15.1)
Language	English
Publishing date	2021-02-18
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202101-0142LE
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Article: ACE2: the node connecting the lung cancer and COVID-19.

Liao, Yan / Zhang, Ying / Li, Houfeng / Hu, Huixiu / Li, Mi / Liao, Chunhua

American journal of cancer research

2024 Volume 14, Issue 4, Page(s) 1466–1481

Abstract: ... Elevated levels of ACE2 in lung cancer patients, which increase the risk of SARS-CoV-2 infection and severe ... of pulmonary fibrosis, chronic inflammation in long-term COVID patients, and the clinical research and mechanisms ... Angiotensin-converting Enzyme 2 (ACE2) collaborates with Angiotensin (Ang) 1-7 and Mas receptors ...

Abstract	Angiotensin-converting Enzyme 2 (ACE2) collaborates with Angiotensin (Ang) 1-7 and Mas receptors to establish the ACE2-Ang (1-7)-Mas receptor axis. ACE2 impacts lung function and can cause lung injury due to its inflammatory effects. Additionally, ACE2 contributes to pulmonary vasculature dysfunction, resulting in pulmonary hypertension. In addition, ACE2 is a receptor for coronavirus entry into host cells, leading to coronavirus infection. Lung cancer, one of the most common respiratory diseases worldwide, has a high rate of infection. Elevated levels of ACE2 in lung cancer patients, which increase the risk of SARS-CoV-2 infection and severe disease, have been demonstrated in clinical studies and by molecular mechanisms. The association between lung cancer and SARS-CoV-2 is closely linked to ACE2. This review examines the basic pathophysiological role of ACE2 in the lung, the long-term effects of SARS-CoV-2 infection on lung function, the development of pulmonary fibrosis, chronic inflammation in long-term COVID patients, and the clinical research and mechanisms underlying the increased susceptibility of lung cancer patients to the virus. Possible mechanisms of lung cancer in SARS-CoV-2-infected individuals and the potential role of ACE2 in this process are also explored in this review. The role of ACE2 as a therapeutic target in the novel coronavirus infection process is also summarized. This will help to inform prevention and treatment of long-term pulmonary complications in patients.
Language	English
Publishing date	2024-04-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2589522-9
ISSN	2156-6976
ISSN	2156-6976
DOI	10.62347/XJVE4569
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Article ; Online: Genetic Landscape of the ACE2 Coronavirus Receptor.

Yang, Zhijian / Macdonald-Dunlop, Erin / Chen, Jiantao / Zhai, Ranran / Li, Ting / Richmond, Anne / Klarić, Lucija / Pirastu, Nicola / Ning, Zheng / Zheng, Chenqing / Wang, Yipeng / Huang, Tingting / He, Yazhou / Guo, Huiming / Ying, Kejun / Gustafsson, Stefan / Prins, Bram / Ramisch, Anna / Dermitzakis, Emmanouil T /

Png, Grace / Eriksson, Niclas / Haessler, Jeffrey / Hu, Xiaowei / Zanetti, Daniela / Boutin, Thibaud / Hwang, Shih-Jen / Wheeler, Eleanor / Pietzner, Maik / Raffield, Laura M / Kalnapenkis, Anette / Peters, James E / Viñuela, Ana / Gilly, Arthur / Elmståhl, Sölve / Dedoussis, George / Petrie, John R / Polašek, Ozren / Folkersen, Lasse / Chen, Yan / Yao, Chen / Võsa, Urmo / Pairo-Castineira, Erola / Clohisey, Sara / Bretherick, Andrew D / Rawlik, Konrad / Esko, Tõnu / Enroth, Stefan / Johansson, Åsa / Gyllensten, Ulf / Langenberg, Claudia / Levy, Daniel / Hayward, Caroline / Assimes, Themistocles L / Kooperberg, Charles / Manichaikul, Ani W / Siegbahn, Agneta / Wallentin, Lars / Lind, Lars / Zeggini, Eleftheria / Schwenk, Jochen M / Butterworth, Adam S / Michaëlsson, Karl / Pawitan, Yudi / Joshi, Peter K / Baillie, J Kenneth / Mälarstig, Anders / Reiner, Alexander P / Wilson, James F / Shen, Xia

Circulation

2022 Volume 145, Issue 18, Page(s) 1398–1411

Abstract: ... We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide ... based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 ... causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian ...

Abstract	Background: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood. Methods: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data. Results: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; Conclusions: Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.
MeSH term(s)	Angiotensin-Converting Enzyme 2/genetics ; COVID-19/genetics ; Cross-Sectional Studies ; Genome-Wide Association Study ; Humans ; Receptors, Coronavirus ; SARS-CoV-2
Chemical Substances	Receptors, Coronavirus ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2022-04-07
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80099-5
ISSN	1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
ISSN (online)	1524-4539
ISSN	0009-7322 ; 0069-4193 ; 0065-8499
DOI	10.1161/CIRCULATIONAHA.121.057888
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Article ; Online: ACE2 Shedding and the Role in COVID-19.

Wang, Jieqiong / Zhao, Huiying / An, Youzhong

Frontiers in cellular and infection microbiology

2022 Volume 11, Page(s) 789180

Abstract: ... used to supplement endogenous ACE2. It may represent a potent COVID-19 treatment in the future ... of the renin-angiotensin system (RAS). In the COVID-19 epidemic, it was found to be the receptor ... of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). ACE2 maintains homeostasis by inhibiting the Ang II-AT1R axis and ...

Abstract	Angiotensin converting enzyme 2 (ACE2), a transmembrane glycoprotein, is an important part of the renin-angiotensin system (RAS). In the COVID-19 epidemic, it was found to be the receptor of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). ACE2 maintains homeostasis by inhibiting the Ang II-AT1R axis and activating the Ang I (1-7)-MasR axis, protecting against lung, heart and kidney injury. In addition, ACE2 helps transport amino acids across the membrane. ACE2 sheds from the membrane, producing soluble ACE2 (sACE2). Previous studies have pointed out that sACE2 plays a role in the pathology of the disease, but the underlying mechanism is not yet clear. Recent studies have confirmed that sACE2 can also act as the receptor of SARS-COV-2, mediating viral entry into the cell and then spreading to the infective area. Elevated concentrations of sACE2 are more related to disease. Recombinant human ACE2, an exogenous soluble ACE2, can be used to supplement endogenous ACE2. It may represent a potent COVID-19 treatment in the future. However, the specific administration concentration needs to be further investigated.
MeSH term(s)	Angiotensin-Converting Enzyme 2 ; COVID-19/drug therapy ; Cell Line ; Humans ; Peptidyl-Dipeptidase A ; SARS-CoV-2
Chemical Substances	Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2022-01-14
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2021.789180
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Article ; Online: Autoantibodies to ACE2 and immune molecules are associated with COVID-19 disease severity.

Geanes, Eric S / McLennan, Rebecca / LeMaster, Cas / Bradley, Todd

Communications medicine

2024 Volume 4, Issue 1, Page(s) 47

Abstract: ... to increased inflammation, severe COVID-19, and long-term complications.: Methods: Here, we deeply profiled ... autoantibody levels are increased in individuals with severe COVID-19 compared with those with mild infection ... levels to ACE2 and other immune factors. The levels of these autoantibodies are associated with COVID-19 ...

Abstract	Background: Increased inflammation caused by SARS-CoV-2 infection can lead to severe coronavirus disease 2019 (COVID-19) and long-term disease manifestations. The mechanisms of this variable long-term immune activation are poorly defined. One feature of this increased inflammation is elevated levels of proinflammatory cytokines and chemokines. Autoantibodies targeting immune factors such as cytokines, as well as the viral host cell receptor, angiotensin-converting enzyme 2 (ACE2), have been observed after SARS-CoV-2 infection. Autoantibodies to immune factors and ACE2 could interfere with normal immune regulation and lead to increased inflammation, severe COVID-19, and long-term complications. Methods: Here, we deeply profiled the features of ACE2, cytokine, and chemokine autoantibodies in samples from patients recovering from severe COVID-19. We measured the levels of immunoglobulin subclasses (IgG, IgA, IgM) in the peripheral blood against ACE2 and 23 cytokines and other immune molecules. We then utilized an ACE2 peptide microarray to map the linear epitopes targeted by ACE2 autoantibodies. Results: We demonstrate that ACE2 autoantibody levels are increased in individuals with severe COVID-19 compared with those with mild infection or no prior infection. We identify epitopes near the catalytic domain of ACE2 targeted by these antibodies. Levels of autoantibodies targeting ACE2 and other immune factors could serve as determinants of COVID-19 disease severity, and represent a natural immunoregulatory mechanism in response to viral infection. Conclusions: These results demonstrate that SARS-CoV-2 infection can increase autoantibody levels to ACE2 and other immune factors. The levels of these autoantibodies are associated with COVID-19 disease severity.
Language	English
Publishing date	2024-03-15
Publishing country	England
Document type	Journal Article
ISSN	2730-664X
ISSN (online)	2730-664X
DOI	10.1038/s43856-024-00477-z
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Article ; Online: FGF7 enhances the expression of ACE2 in human islet organoids aggravating SARS-CoV-2 infection.

Meng, Hao / Liao, Zhiying / Ji, Yanting / Wang, Dong / Han, Yang / Huang, Chaolin / Hu, Xujuan / Chen, Jingyi / Zhang, Hengrui / Li, Zonghong / Wang, Changliang / Sun, Hui / Sun, Jiaqi / Chen, Lihua / Yin, Jiaxiang / Zhao, Jincun / Xu, Tao / Liu, Huisheng

Signal transduction and targeted therapy

2024 Volume 9, Issue 1, Page(s) 104

Abstract: ... in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 ... strategy against COVID-19. In the current study, we utilized islet organoids derived from human ... embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7 ...

Abstract	The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in β cells. This upregulation increases both insulin secretion and susceptibility of β cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.
MeSH term(s)	Animals ; Humans ; Male ; Mice ; Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/genetics ; COVID-19/metabolism ; COVID-19/virology ; COVID-19/pathology ; Fibroblast Growth Factor 7/genetics ; Fibroblast Growth Factor 7/metabolism ; Human Embryonic Stem Cells/metabolism ; Insulin Secretion/genetics ; Islets of Langerhans/metabolism ; Islets of Langerhans/virology ; Islets of Langerhans/pathology ; Organoids/virology ; Organoids/metabolism ; Organoids/pathology ; SARS-CoV-2/genetics
Language	English
Publishing date	2024-04-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2886872-9
ISSN	2059-3635 ; 2095-9907
ISSN (online)	2059-3635
ISSN	2095-9907
DOI	10.1038/s41392-024-01790-8
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Article ; Online: Raman spectroscopy study of 7,8-dihydrofolate inhibition on the Wuhan strain SARS-CoV-2 binding to human ACE2 receptor.

Galván-Ojeda, Hiram Joazet / Acosta-Elias, Jesus / Saavedra-Alanis, Victor M / Espinosa-Tanguma, Ricardo / Del Carmen Rodríguez-Aranda, Ma / Hernández-Arteaga, Aida Catalina / Navarro-Contreras, Hugo Ricardo

Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy

2024 Volume 312, Page(s) 124050

Abstract: ... the severity of Covid-19 among hospitalized patients. Yet, the underlying mechanisms governing this intriguing ... comprehensive studies of COVID-19 patients in Israel and UK uncovered a remarkable trend, wherein individuals ... therapeutic strategies in the battle against COVID-19 and reinforces the significance of investigating ...

Abstract	Emerging evidence suggests that elevated levels of folic acid in the bloodstream may confer protection against Wuhan-SARS-CoV-2 infection and mitigate its associated symptoms. Notably, two comprehensive studies of COVID-19 patients in Israel and UK uncovered a remarkable trend, wherein individuals with heightened folic acid levels exhibited only mild symptoms and necessitated no ventilatory support. In parallel, research has underscored the potential connection between decreased folic acid levels and the severity of Covid-19 among hospitalized patients. Yet, the underlying mechanisms governing this intriguing inhibition remain elusive. In a quest to elucidate these mechanisms, we conducted a molecular dynamics simulation approach followed by a Raman spectroscopy study to delve into the intricate interplay between the folic acid metabolite, 7,8-dihydrofolate (DHF), and the angiotensin-converting enzyme ACE2 receptor, coupled with its interaction with the receptor-binding domain (RBD) of the Wuhan strain of SARS-CoV-2. Through a meticulous exploration, we scrutinized the transformation of the ACE2 + RBD complex, allowing these reactants to form bonds. This was juxtaposed with a similar investigation where ACE2 was initially permitted to react with DHF, followed by the exposure of the ACE2 + DHF complex to RBD. We find that DHF, when bonded to ACE2, functions as a physical barrier, effectively inhibiting the binding of the Wuhan strain RBD. This physicochemical process offers a cogent explanation for the observed inhibition of host cell infection in subjects receiving supplementary folic acid doses, as epidemiologically substantiated in multiple studies. This study not only sheds light on a potential avenue for mitigating SARS-CoV-2 infection but also underscores the crucial role of folic acid metabolites in host-virus interactions. This research paves the way for novel therapeutic strategies in the battle against COVID-19 and reinforces the significance of investigating the molecular mechanisms underlying the protective effects of folic acid in the context of viral infections.
MeSH term(s)	Humans ; Angiotensin-Converting Enzyme 2 ; COVID-19 ; Folic Acid/analogs & derivatives ; Folic Acid/metabolism ; Folic Acid/pharmacology ; Molecular Dynamics Simulation ; Protein Binding ; SARS-CoV-2 ; Spectrum Analysis, Raman
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; dihydrofolate (4033-27-6) ; Folic Acid (935E97BOY8)
Language	English
Publishing date	2024-02-20
Publishing country	England
Document type	Journal Article
ZDB-ID	210413-1
ISSN	1873-3557 ; 0370-8322 ; 0584-8539 ; 1386-1425
ISSN (online)	1873-3557
ISSN	0370-8322 ; 0584-8539 ; 1386-1425
DOI	10.1016/j.saa.2024.124050
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Article ; Online: Level of the SARS-CoV-2 receptor ACE2 activity is highly elevated in old-aged patients with aortic stenosis: implications for ACE2 as a biomarker for the severity of COVID-19.

Fagyas, Miklós / Kertész, Attila / Siket, Ivetta Mányiné / Bánhegyi, Viktor / Kracskó, Bertalan / Szegedi, Andrea / Szokol, Miklós / Vajda, Gusztáv / Rácz, Ildikó / Gulyás, Hajnalka / Szkibák, Noémi / Rácz, Vivienn / Csanádi, Zoltán / Papp, Zoltán / Tóth, Attila / Sipka, Sándor

GeroScience

2021 Volume 43, Issue 1, Page(s) 19–29

Abstract: ... cardiovascular complications in the elderly, a prime condition for COVID-19 mortality. The circulating ACE2 ... circulating ACE2 as a potential interface between chronic inflammation, cardiovascular disease, and COVID-19 ... Coronavirus disease 2019 (COVID-19) has a high mortality in elderly patients with pre-existing ...

Abstract	Coronavirus disease 2019 (COVID-19) has a high mortality in elderly patients with pre-existing cardiovascular diseases. The cellular receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the angiotensin-converting enzyme 2 (ACE2), thereby implicating a link between cardiovascular diseases and SARS-CoV-2 susceptibility. Aortic stenosis (AS) represents a chronic inflammatory state with severe cardiovascular complications in the elderly, a prime condition for COVID-19 mortality. The circulating ACE2 levels were measured in 111 patients with severe AS and compared to patients with hypertension and healthy individuals. About 4 times higher circulating ACE2 activity was found in patients with severe AS than in hypertensives or healthy individuals (88.3 ± 61.6., n = 111, 20.6 ± 13.4, n = 540, and 16.1 ± 7.4 mU/L, n = 46, respectively). Patients with severe AS were older than patients with hypertension (80 ± 6 years vs. 60 ± 15 years, P < 0.05). Serum ACE2 activity correlated negatively with the left ventricular ejection fraction, aortic root area, TAPSE, and positively with the right ventricular systolic pressure, cardiac diameters in patients with AS. In contrast, circulating ACE2 activity was independent of the blood pressure, peak flow velocity at the aortic root, kidney function (GFR), and inflammatory state (CRP). We found no effect of RAAS inhibitory drugs on the serum ACE2 activity in this group of patients. Our results illustrate circulating ACE2 as a potential interface between chronic inflammation, cardiovascular disease, and COVID-19 susceptibility. Elderly patients with AS have markedly elevated ACE2 levels together with altered left and right ventricular functions, which may pose higher risks during COVID-19. Our clinical data do not support a role for RAAS inhibitors in regulating circulating ACE2 levels.
MeSH term(s)	Aged ; Angiotensin-Converting Enzyme 2 ; Aortic Valve Stenosis ; Biomarkers ; COVID-19 ; Humans ; Middle Aged ; Peptidyl-Dipeptidase A ; Renin-Angiotensin System ; SARS-CoV-2 ; Stroke Volume ; Ventricular Function, Left
Chemical Substances	Biomarkers ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2021-01-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-020-00300-2
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Article ; Online: Elevated angiotensin-converting enzyme 2 (ACE2) expression in cats with hypertrophic cardiomyopathy.

Lean, Fabian Z X / Priestnall, Simon L / Vitores, Ana Gómez / Suárez-Bonnet, Alejandro / Brookes, Sharon M / Núñez, Alejandro

Research in veterinary science

2022 Volume 152, Page(s) 564–568

Abstract: ... with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) acquired from human patients, a previous study has suggested ... hypertrophic cardiomyopathy (HCM) is a potential risk factor for the development of severe disease in the cat. Herein ... Angiotensin-converting enzyme 2 (ACE2) is an enzyme within the renin-angiotensin-aldosterone system ...

Abstract	Angiotensin-converting enzyme 2 (ACE2) is an enzyme within the renin-angiotensin-aldosterone system that plays a role in regulating blood pressure. However, it is also a cellular receptor for infection with SARS coronaviruses. Although most cats develop subclinical or mild disease following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) acquired from human patients, a previous study has suggested hypertrophic cardiomyopathy (HCM) is a potential risk factor for the development of severe disease in the cat. Herein we investigate the ACE2 protein expression in the lung, heart, and kidney from a small subset of cats with (n = 10) and without HCM (n = 10) by immunohistochemistry. The abundance and intensity of ACE2 expression is slightly elevated in alveoli (p = 0.09; 0.07, respectively) and bronchioles (p = 0.095; 0.37, respectively). However, statistically elevated abundance and intensity of ACE-2 expression was only evident in the heart of cats with HCM (p = 0.032; p = 0.011, respectively). Further investigation did not demonstrate a statistical correlation between the ACE2 expression in the heart in relation to the heart weight to body weight ratio, and the ventricular wall ratio. Current findings suggest an overexpression of ACE2 in HCM cases but follow up study is warranted to understand the pathophysiological process.
MeSH term(s)	Humans ; Cats ; Animals ; Angiotensin-Converting Enzyme 2/genetics ; SARS-CoV-2 ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/metabolism ; Follow-Up Studies ; COVID-19/veterinary ; Renin-Angiotensin System ; Cardiomyopathy, Hypertrophic/genetics ; Cardiomyopathy, Hypertrophic/veterinary ; Cardiomyopathy, Hypertrophic/metabolism ; Cat Diseases
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Peptidyl-Dipeptidase A (EC 3.4.15.1)
Language	English
Publishing date	2022-09-27
Publishing country	England
Document type	Journal Article
ZDB-ID	840961-4
ISSN	1532-2661 ; 0034-5288
ISSN (online)	1532-2661
ISSN	0034-5288
DOI	10.1016/j.rvsc.2022.09.024
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Article ; Online: Circulating ACE2 level and zinc/albumin ratio as potential biomarkers for a precision medicine approach to COVID-19.

Benedetti, Serena / Sisti, Davide / Vandini, Daniela / Barocci, Simone / Sudano, Maurizio / Carlotti, Eugenio / Teng, Jade Lee Lee / Zamai, Loris

Advances in biological regulation

2023 Volume 89, Page(s) 100973

Abstract: ... precision medicine to COVID-19, circulating ACE2 has potential features being upregulated in both severe ... positive feedback loops leading to COVID-19-like manifestations. For this reason, pre-existing ACE2 ... COVID-19-susceptible) and SARS-CoV-2-negative COVID-19 individuals. ACE2 both protein levels and ...

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.
MeSH term(s)	Humans ; COVID-19/genetics ; SARS-CoV-2/genetics ; SARS-CoV-2/metabolism ; Renin-Angiotensin System/physiology ; Angiotensin-Converting Enzyme 2/genetics ; Peptidyl-Dipeptidase A ; Precision Medicine ; Zinc/therapeutic use ; Albumins/metabolism ; Biomarkers
Chemical Substances	Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Zinc (J41CSQ7QDS) ; Albumins ; Biomarkers
Language	English
Publishing date	2023-05-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2667413-0
ISSN	2212-4934 ; 2212-4926
ISSN (online)	2212-4934
ISSN	2212-4926
DOI	10.1016/j.jbior.2023.100973
Database	MEDical Literature Analysis and Retrieval System OnLINE

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