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  1. Article ; Online: Renin-Angiotensin System and Sex Differences in COVID-19: A Critical Assessment.

    Chappell, Mark C

    Circulation research

    2023  Volume 132, Issue 10, Page(s) 1320–1337

    Abstract: The current epidemic of corona virus disease (COVID-19) has resulted in an immense health burden that became the third leading cause of death and potentially contributed to a decline in life expectancy in the United States. The severe acute respiratory ... ...

    Abstract The current epidemic of corona virus disease (COVID-19) has resulted in an immense health burden that became the third leading cause of death and potentially contributed to a decline in life expectancy in the United States. The severe acute respiratory syndrome-related coronavirus-2 binds to the surface-bound peptidase angiotensin-converting enzyme 2 (ACE2, EC 3.4.17.23) leading to tissue infection and viral replication. ACE2 is an important enzymatic component of the renin-angiotensin system (RAS) expressed in the lung and other organs. The peptidase regulates the levels of the peptide hormones Ang II and Ang-(1-7), which have distinct and opposing actions to one another, as well as other cardiovascular peptides. A potential consequence of severe acute respiratory syndrome-related coronavirus-2 infection is reduced ACE2 activity by internalization of the viral-ACE2 complex and subsequent activation of the RAS (higher ratio of Ang II:Ang-[1-7]) that may exacerbate the acute inflammatory events in COVID-19 patients and possibly contribute to the effects of long COVID-19. Moreover, COVID-19 patients present with an array of autoantibodies to various components of the RAS including the peptide Ang II, the enzyme ACE2, and the AT
    MeSH term(s) Humans ; Male ; Female ; Renin-Angiotensin System/physiology ; COVID-19 ; Angiotensin-Converting Enzyme 2/metabolism ; Peptidyl-Dipeptidase A/physiology ; SARS-CoV-2 ; Sex Characteristics ; Post-Acute COVID-19 Syndrome ; Angiotensin-Converting Enzyme Inhibitors/pharmacology
    Chemical Substances Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; Angiotensin-Converting Enzyme Inhibitors
    Language English
    Publishing date 2023-05-11
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/CIRCRESAHA.123.321883
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: S1P (Site-1 Protease)-Induced Release of the Soluble Prorenin Receptor in Hypertension: Do All Roads Lead to Ang II (Angiotensin II)?

    Chappell, Mark C

    Hypertension (Dallas, Tex. : 1979)

    2021  Volume 77, Issue 2, Page(s) 417–419

    MeSH term(s) Angiotensin II ; Humans ; Hypertension ; Proprotein Convertases ; Receptors, Cell Surface ; Serine Endopeptidases
    Chemical Substances Receptors, Cell Surface ; prorenin receptor ; Angiotensin II (11128-99-7) ; Proprotein Convertases (EC 3.4.21.-) ; Serine Endopeptidases (EC 3.4.21.-) ; membrane-bound transcription factor peptidase, site 1 (EC 3.4.21.112)
    Language English
    Publishing date 2021-01-14
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.120.16428
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  3. Article ; Online: Commentary for "Endocrine significance of SARS-CoV-2's Reliance on ACE2".

    Chappell, Mark C

    Endocrinology

    2020  Volume 162, Issue 4

    MeSH term(s) COVID-19 ; Humans ; Peptidyl-Dipeptidase A/metabolism ; Renin-Angiotensin System ; SARS-CoV-2
    Chemical Substances Peptidyl-Dipeptidase A (EC 3.4.15.1)
    Language English
    Publishing date 2020-11-30
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/endocr/bqaa222
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  4. Article ; Online: Gut dysbiosis and hypertension: is it cause or effect?

    Cook, Katherine L / Chappell, Mark C

    Journal of hypertension

    2021  Volume 39, Issue 9, Page(s) 1768–1770

    MeSH term(s) Dysbiosis ; Gastrointestinal Microbiome ; Humans ; Hypertension
    Language English
    Publishing date 2021-07-20
    Publishing country England
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Comment
    ZDB-ID 605532-1
    ISSN 1473-5598 ; 0263-6352 ; 0952-1178
    ISSN (online) 1473-5598
    ISSN 0263-6352 ; 0952-1178
    DOI 10.1097/HJH.0000000000002908
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Hydrogen sulfide, then nitric oxide and vasoprotection.

    Chappell, Mark C

    Journal of hypertension

    2018  Volume 36, Issue 3, Page(s) 493–494

    MeSH term(s) Humans ; Hydrogen Sulfide ; Hypertension ; Nitric Oxide ; Nitric Oxide Synthase Type III ; PPAR delta
    Chemical Substances PPAR delta ; Nitric Oxide (31C4KY9ESH) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; Hydrogen Sulfide (YY9FVM7NSN)
    Language English
    Publishing date 2018-09-04
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 605532-1
    ISSN 1473-5598 ; 0263-6352 ; 0952-1178
    ISSN (online) 1473-5598
    ISSN 0263-6352 ; 0952-1178
    DOI 10.1097/HJH.0000000000001617
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  6. Article ; Online: Reply to "Letter to the editor: Angiotensin quantification by mass spectrometry".

    Chappell, Mark C

    American journal of physiology. Heart and circulatory physiology

    2016  Volume 310, Issue 3, Page(s) H454

    MeSH term(s) Animals ; Humans ; Renin-Angiotensin System/physiology
    Language English
    Publishing date 2016-02-01
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 603838-4
    ISSN 1522-1539 ; 0363-6135
    ISSN (online) 1522-1539
    ISSN 0363-6135
    DOI 10.1152/ajpheart.00960.2015
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  7. Article ; Online: Amiloride and the diabetic kidney.

    Chappell, Mark C

    Journal of hypertension

    2016  Volume 34, Issue 8, Page(s) 1500–1501

    MeSH term(s) Amiloride ; Diabetes Mellitus ; Humans ; Kidney ; Sodium
    Chemical Substances Amiloride (7DZO8EB0Z3) ; Sodium (9NEZ333N27)
    Language English
    Publishing date 2016-06-27
    Publishing country England
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 605532-1
    ISSN 1473-5598 ; 0263-6352 ; 0952-1178
    ISSN (online) 1473-5598
    ISSN 0263-6352 ; 0952-1178
    DOI 10.1097/HJH.0000000000001031
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  8. Article ; Online: The Angiotensin-(1-7) Axis: Formation and Metabolism Pathways

    Chappell, Mark C.

    Angiotensin-(1-7)

    Abstract: The renin-angiotensin system (RAS) constitutes a key hormonal system in the physiological regulation of blood pressure via peripheral and central mechanisms. Dysregulation of the RAS is considered a major factor in the development of cardiovascular ... ...

    Abstract The renin-angiotensin system (RAS) constitutes a key hormonal system in the physiological regulation of blood pressure via peripheral and central mechanisms. Dysregulation of the RAS is considered a major factor in the development of cardiovascular pathologies and pharmacologic blockade of this system by the inhibition of angiotensin-converting enzyme (ACE) or antagonism of the angiotensin type 1 receptor (AT(1)R) is an effective therapeutic regimen. The RAS is now defined as a more complex system composed of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS comprises the ACE-Ang II-AT(1)R axis that promotes vasoconstriction, water intake, sodium retention and increased oxidative stress, fibrosis, cellular growth, and inflammation. The non-classical or alternative RAS is composed primarily of the ACE2-Ang-(1-7)-AT(7)R pathway that opposes many actions of the Ang II-AT(1)R axis. In lieu of the complexity of this system, the chapter discusses the current evidence on the enzymatic cascade of the Ang-(1-7) axis of the RAS regarding the peptidases that contribute to the formation and degradation of the peptide in the circulation and various tissues.
    Keywords covid19
    Publisher PMC
    Document type Article ; Online
    DOI 10.1007/978-3-030-22696-1_1
    Database COVID19

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  9. Article ; Online: The Renin-Angiotensin-Aldosterone System in COVID-19-related and Non-COVID-19-related Acute Respiratory Distress Syndrome: Not So Different after All?

    Collins, Sean P / Chappell, Mark C / Files, D Clark

    American journal of respiratory and critical care medicine

    2021  Volume 204, Issue 9, Page(s) 1007–1008

    MeSH term(s) Angiotensin Receptor Antagonists ; COVID-19 ; Humans ; Renin-Angiotensin System ; Respiratory Distress Syndrome ; SARS-CoV-2
    Chemical Substances Angiotensin Receptor Antagonists
    Language English
    Publishing date 2021-09-02
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 1180953-x
    ISSN 1535-4970 ; 0003-0805 ; 1073-449X
    ISSN (online) 1535-4970
    ISSN 0003-0805 ; 1073-449X
    DOI 10.1164/rccm.202108-1904ED
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  10. Article ; Online: Dysfunction of the renin-angiotensin-aldosterone system in human septic shock.

    Schaich, Christopher L / Leisman, Daniel E / Goldberg, Marcia B / Filbin, Micheal R / Khanna, Ashish K / Chappell, Mark C

    Peptides

    2024  Volume 176, Page(s) 171201

    Abstract: Sepsis and septic shock are global healthcare problems associated with mortality rates of up to 40% despite optimal standard-of-care therapy and constitute the primary cause of death in intensive care units worldwide. Circulating biomarkers of septic ... ...

    Abstract Sepsis and septic shock are global healthcare problems associated with mortality rates of up to 40% despite optimal standard-of-care therapy and constitute the primary cause of death in intensive care units worldwide. Circulating biomarkers of septic shock severity may represent a clinically relevant approach to individualize those patients at risk for worse outcomes early in the course of the disease, which may facilitate early and more precise interventions to improve the clinical course. However, currently used septic shock biomarkers, including lactate, may be non-specific and have variable impact on prognosis and/or disease management. Activation of the renin-angiotensin-aldosterone system (RAAS) is likely an early event in septic shock, and studies suggest that an elevated level of renin, the early and committed step in the RAAS cascade, is a better predictor of worse outcomes in septic shock, including mortality, than the current standard-of-care measure of lactate. Despite a robust increase in renin, other elements of the RAAS, including endogenous levels of Ang II, may fail to sufficiently increase to maintain blood pressure, tissue perfusion, and protective immune responses in septic shock patients. We review the current clinical literature regarding the dysfunction of the RAAS in septic shock and potential therapeutic approaches to improve clinical outcomes.
    Language English
    Publishing date 2024-03-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 769028-9
    ISSN 1873-5169 ; 0196-9781
    ISSN (online) 1873-5169
    ISSN 0196-9781
    DOI 10.1016/j.peptides.2024.171201
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