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Endocrine aspects of ACE2 regulation : RAAS, steroid hormones and SARS-CoV-2

Coronavirus disease (COVID-19) is caused by a new strain of coronavirus, the severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2. At the time of writing, SARS-CoV-2 has infected over 5 million people worldwide. A key step in understanding the pathobiology of the SARS-CoV-2 was the identification of -converting enzyme 2 (ACE2) as the receptor for SARS-CoV-2 to gain entry into host cells. ACE2 is an established component of the 'protective arm' of the renin-angiotensin-aldosterone-system (RAAS) that opposes ACE/angiotensin II (ANG II) pressor and tissue remodelling actions. Identification of ACE2 as the entry point for SARS-CoV-2 into cells quickly focused attention on the use of ACE inhibitors (ACEi), angiotensin receptor blockers (ARB) and mineralocorticoid receptor antagonists (MRA) in patients with hypertension and cardiovascular disease given that these pharmacological agents upregulate ACE2 expression in target cells. ACE2 is cleaved from the cells by metalloproteases ADAM10 and ADAM17. Steroid hormone receptors regulate multiple components of the RAAS and may contribute to the observed variation in the incidence of severe COVID-19 between men and women, and in patients with pre-existing endocrine-related disease. Moreover, glucocorticoids play a critical role in the acute and chronic management of inflammatory disease, independent of any effect on RAAS activity. Dexamethasone, a synthetic glucocorticoid, has emerged as a life-saving treatment in severe COVID-19. This review will examine the endocrine mechanisms that control ACE2 and discusses the impact of therapies targeting the RAAS, glucocorticoid and other endocrine systems for their relevance to the impact of SARS-CoV-2 infection and the treatment and recovery from COVID-19-related critical illness

Year of Publication: 2020
Contained in: The Journal of endocrinology Vol. 247, No. 2 (2020), p. R45-R62
All journal articles: Search for all articles in this journal
Language: English
Contributors: Young, Morag J | Author
Clyne, Colin D
Chapman, Karen E
Full text access:
Electronic availability is being checked...
Links: Full Text (dx.doi.org)
Keywords: 4964P6T9RB
ACE2
COVID-19
EC 3.4.15.1
EC 3.4.17.-
Journal Article
Research Support, Non-U.S. Gov't
Review
SARS-CoV-2
angiotensin converting enzyme 2
angiotensin
corticosteroid
dexamethasone
glucocorticoid receptor
nuclear receptor
Additional Keywords: *Renin-Angiotensin System
Aldosterone
Angiotensin-Converting Enzyme Inhibitors
Animals
Betacoronavirus
Coronavirus Infections
Humans
Pandemics
Peptidyl-Dipeptidase A
Pneumonia, Viral
Receptors, Steroid
Steroids
ISSN: 1479-6805
Note: Copyright: From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Notes: Date Completed 01.10.2020
Date Revised 01.10.2020
published: Print
Citation Status MEDLINE
Copyright: From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
PMID:
    32966970
Physical Description: Online-Ressource
ID (e.g. DOI, URN): 10.1530/JOE-20-0260
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