The Counter Regulatory Axis of the Lung Renin-Angiotensin System in Severe COVID-19: Pathophysiology and Clinical Implications.
Heart Lung Circ
; 30(6): 786-794, 2021 Jun.
Article
in English
| MEDLINE | ID: covidwho-1217564
ABSTRACT
The severe acute respiratory syndrome coronavirus (SARS-CoV)-2, which is responsible for coronavirus disease 2019 (COVID-19), uses angiotensin (ANG)-converting enzyme 2 (ACE2) as the entrance receptor. Although most COVID-19 cases are mild, some are severe or critical, predominantly due to acute lung injury. It has been widely accepted that a counter regulatory renin-angiotensin system (RAS) axis including the ACE2/ANG [1-7]/Mas protects the lungs from acute lung injury. However, recent evidence suggests that the generation of protective ANG [1-7] in the lungs is predominantly mediated by proinflammatory prolyl oligopeptidase (POP), which has been repeatedly demonstrated to be involved in lung pathology. This review contends that acute lung injury in severe COVID-19 is characterised by a) ACE2 downregulation and malfunction (inflammatory signalling) due to viral occupation, and b) dysregulation of the protective RAS axis, predominantly due to increased activity of proinflammatory POP. It follows that a reasonable treatment strategy in COVID-19-related acute lung injury would be delivering functional recombinant (r) ACE2 forms to trap the virus. Additionally, or alternatively to rACE2 delivery, the potential benefits resulting from lowering POP activity should also be explored. These treatment strategies deserve further investigation.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Renin-Angiotensin System
/
Signal Transduction
/
Acute Lung Injury
/
Angiotensin-Converting Enzyme 2
/
COVID-19
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Heart Lung Circ
Journal subject:
Vascular Diseases
/
Cardiology
Year:
2021
Document Type:
Article
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