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  1. Article ; Online: Expression of ACE2, Soluble ACE2, Angiotensin I, Angiotensin II and Angiotensin-(1-7) Is Modulated in COVID-19 Patients.

    Osman, Ikram Omar / Melenotte, Cléa / Brouqui, Philippe / Million, Matthieu / Lagier, Jean-Christophe / Parola, Philippe / Stein, Andréas / La Scola, Bernard / Meddeb, Line / Mege, Jean-Louis / Raoult, Didier / Devaux, Christian A

    Frontiers in immunology

    2021  Volume 12, Page(s) 625732

    Abstract: ... variations of ACE2 expression and Ang II plasma concentration in SARS-CoV-2-infected patients. We report here ... Ang II) into Angiotensin-(1-7) [Ang-(1-7)]. We therefore hypothesized that SARS-CoV-2 could trigger ... that circulating blood cells from COVID-19 patients express less ACE2 mRNA than cells from healthy volunteers ...

    Abstract The etiological agent of COVID-19 SARS-CoV-2, is primarily a pulmonary-tropic coronavirus. Infection of alveolar pneumocytes by SARS-CoV-2 requires virus binding to the angiotensin I converting enzyme 2 (ACE2) monocarboxypeptidase. ACE2, present on the surface of many cell types, is known to be a regulator of blood pressure homeostasis through its ability to catalyze the proteolysis of Angiotensin II (Ang II) into Angiotensin-(1-7) [Ang-(1-7)]. We therefore hypothesized that SARS-CoV-2 could trigger variations of ACE2 expression and Ang II plasma concentration in SARS-CoV-2-infected patients. We report here, that circulating blood cells from COVID-19 patients express less ACE2 mRNA than cells from healthy volunteers. At the level of circulating cells, this
    MeSH term(s) Adult ; Angiotensin I/blood ; Angiotensin II/blood ; Angiotensin-Converting Enzyme 2/blood ; Angiotensin-Converting Enzyme 2/genetics ; COVID-19/blood ; COVID-19/virology ; Female ; Gene Expression Profiling ; HLA-DR Antigens ; Humans ; Lipopolysaccharide Receptors ; Male ; Middle Aged ; Monocytes/immunology ; Monocytes/metabolism ; Peptide Fragments/blood ; Pilot Projects ; Prospective Studies ; RNA, Messenger ; Virus Shedding
    Chemical Substances CD14 protein, human ; HLA-DR Antigens ; Lipopolysaccharide Receptors ; Peptide Fragments ; RNA, Messenger ; Angiotensin II (11128-99-7) ; Angiotensin I (9041-90-1) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; angiotensin I (1-7) (IJ3FUK8MOF)
    Language English
    Publishing date 2021-06-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2021.625732
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Expression of ACE2 receptor, soluble ACE2, Angiotensin I, Angiotensin II and Angiotensin (1-7), is modulated in COVID-19 patients.

    OSMAN, Ikram Omar / Menelotte, Clea / Brouqui, Philippe / MILLION, Matthieu / LAGIER, Jean-christophe / PAROLA, Phillipe / STEIN, Andreas / LA SCOLA, Bernard / MEDDEB, Line / MEGE, Jean-Louis / RAOULT, Didier / DEVAUX, Christian Albert

    medRxiv

    Abstract: ... replication in COVID-19 patients could modulate the expression of the ACE2 receptor and/or the AngII plasma ... levels. We demonstrate here, that in COVID-19 patients the ACE2 mRNA expression is markedly reduced ... On the other hand, the plasma levels of Ang(1-7) remains almost stable in COVID-19 patients. Despite the Ang(1-7 ...

    Abstract Although SARS-CoV-2 is primarily a pulmonary-tropic virus, it is nonetheless responsible for multi-organ failure in patients with severe forms of COVID-19, particularly those with hypertension or cardiovascular disease. Infection requires virus binding to the angiotensin I converting enzyme 2 (ACE2) monocarboxypeptidase, a regulator of blood pressure homeostasis through its ability to catalyze the proteolysis of Angiotensin II (AngII) into Ang(1-7). Although assumed, it had not been proven so far whether the SARS-CoV-2 replication in COVID-19 patients could modulate the expression of the ACE2 receptor and/or the AngII plasma levels. We demonstrate here, that in COVID-19 patients the ACE2 mRNA expression is markedly reduced in circulating blood cells. This ACE2 gene dysregulation mainly affects the monocytes which also show a lower expression of membrane ACE2 protein. Moreover, a significant decrease in soluble ACE2 plasma levels is observed in COVID-19 patients, whereas the concentration of sACE2 returns to normal levels in patients recovered from COVID-19. In the plasma of COVID-19 patients, we also found an increase in AngI and AngII. On the other hand, the plasma levels of Ang(1-7) remains almost stable in COVID-19 patients. Despite the Ang(1-7) presence in the plasma of COVID-19 patients it seems insufficient to prevent the effects of massive AngII accumulation. These are the first direct evidence that the SARS-CoV-2 may affect the expression of blood pressure regulators with possible harmful consequences on COVID-19 outcome.
    Keywords covid19
    Language English
    Publishing date 2021-02-10
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2021.02.08.21251001
    Database COVID19

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  3. Article ; Online: Interactions of renin-angiotensin system and COVID-19: the importance of daily rhythms in ACE2, ADAM17 and TMPRSS2 expression.

    Zlacká, J / Stebelová, K / Zeman, M / Herichová, I

    Physiological research

    2022  Volume 70, Issue S2, Page(s) S177–S194

    Abstract: ... from angiotensin II (Ang II), suppressed ACE2 levels in the lung can contribute to secondary COVID-19 complications ... associated with suppressed activity of ACE2. As a major role of ACE2 is to form vasodilatory angiotensin 1-7 ... association of hypertension and negative COVID-19 prognosis although this relationship is dependent ...

    Abstract Angiotensin-converting enzyme 2 (ACE2) was identified as a molecule that mediates the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several membrane molecules of the host cell must cooperate in this process. While ACE2 serves in a membrane receptor-mediating interaction with the surface spike (S) glycoprotein of SARS-CoV-2 located on the virus envelope, enzyme A disintegrin and metalloproteinase 17 (ADAM17) regulates ACE2 availability on the membrane and transmembrane protease serine 2 (TMPRSS2) facilitates virus-cell membrane fusion. Interestingly, ACE2, ADAM17 and TMPRSS2 show a daily rhythm of expression in at least some mammalian tissue. The circadian system can also modulate COVID-19 progression via circadian control of the immune system (direct, as well as melatonin-mediated) and blood coagulation. Virus/ACE2 interaction causes ACE2 internalization into the cell, which is associated with suppressed activity of ACE2. As a major role of ACE2 is to form vasodilatory angiotensin 1-7 from angiotensin II (Ang II), suppressed ACE2 levels in the lung can contribute to secondary COVID-19 complications caused by up-regulated, pro-inflammatory vasoconstrictor Ang II. This is supported by the positive association of hypertension and negative COVID-19 prognosis although this relationship is dependent on numerous comorbidities. Hypertension treatment with inhibitors of renin-angiotensin system does not negatively influence prognosis of COVID-19 patients. It seems that tissue susceptibility to SARS-CoV-2 shows negative correlation to ACE2 expression. However, in lungs of infected patient, a high ACE2 expression is associated with better outcome, compared to low ACE2 expression. Manipulation of soluble ACE2 levels is a promising COVID-19 therapeutic strategy.
    MeSH term(s) ADAM17 Protein/metabolism ; Angiotensin-Converting Enzyme 2/metabolism ; Animals ; COVID-19/metabolism ; COVID-19/physiopathology ; COVID-19/therapy ; COVID-19/virology ; Circadian Rhythm ; Host-Pathogen Interactions ; Humans ; Hypertension/metabolism ; Hypertension/physiopathology ; Periodicity ; Prognosis ; Renin-Angiotensin System ; SARS-CoV-2/metabolism ; SARS-CoV-2/pathogenicity ; Serine Endopeptidases/metabolism ; Signal Transduction ; Time Factors
    Chemical Substances ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-) ; ADAM17 Protein (EC 3.4.24.86) ; ADAM17 protein, human (EC 3.4.24.86)
    Language English
    Publishing date 2022-01-03
    Publishing country Czech Republic
    Document type Journal Article ; Review
    ZDB-ID 1073141-6
    ISSN 1802-9973 ; 0369-9463 ; 0862-8408
    ISSN (online) 1802-9973
    ISSN 0369-9463 ; 0862-8408
    DOI 10.33549/physiolres.934754
    Database MEDical Literature Analysis and Retrieval System OnLINE

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