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.

Media Type:

Electronic Article

Year of Publication:

2020

Contained In:

The Journal of endocrinology - Vol. 247, No. 2 (2020), p. R45-R62

Language:

English

Contributors:

Young, Morag J
Clyne, Colin D
Chapman, Karen E

Links:

Volltext

Keywords:

*Renin-Angiotensin System
4964P6T9RB
ACE2
Aldosterone
Angiotensin
Angiotensin converting enzyme 2
Angiotensin-Converting Enzyme Inhibitors
Animals
Betacoronavirus
COVID-19
Coronavirus Infections
Corticosteroid
Dexamethasone
EC 3.4.15.1
EC 3.4.17.-
Glucocorticoid receptor
Humans
Journal Article
Nuclear receptor
Pandemics
Peptidyl-Dipeptidase A
Pneumonia, Viral
Receptors, Steroid
Research Support, Non-U.S. Gov't
Review
SARS-CoV-2
Steroids

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

Physical Description:

Online-Ressource

doi:

10.1530/JOE-20-0260

PMID:

32966970

PPN (Catalogue-ID):

NLM31633930X