The Counter Regulatory Axis of the Lung Renin-Angiotensin System in Severe COVID-19: Pathophysiology and Clinical Implications - 04/05/21

Doi : 10.1016/j.hlc.2020.11.008

Filippos Triposkiadis, MD ^a,^⁎ , Randall C. Starling, MD, MPH ^b, Andrew Xanthopoulos, MD ^a, Javed Butler, MD, MPH ^c, Harisios Boudoulas, MD ^d
^a Department of Cardiology, Larissa University General Hospital, Larissa, Greece
^b Kaufman Center for Heart Failure and Recovery, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA
^c Department of Medicine, University of Mississippi, Jackson, MS, USA
^d Department of Medicine/Cardiovascular Medicine, The Ohio State University, Columbus, OH, USA

^∗Corresponding author at: Professor of Cardiology, University of Thessaly, Director, Department of Cardiology, Larissa University Hospital, PO Box 1425, 411 10 Larissa, GreeceProfessor of CardiologyUniversity of Thessaly, Director, Department of CardiologyLarissa University HospitalPO Box 1425Larissa411 10Greece

connectez-vous ou créez un compte

Bienvenue sur EM-consulte, la référence des professionnels de santé.
Article gratuit.

Connectez-vous pour en bénéficier!

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.

Le texte complet de cet article est disponible en PDF.

Highlights

•	Severe acute respiratory syndrome coronavirus (SARS-CoV)-2, which is responsible for coronavirus disease 2019 (COVID-19), uses angiotensin-converting enzyme 2 (ACE2) as the entrance receptor.
•	The pathophysiology of severe COVID-19 is predominated by severe acute lung injury.
•	In the lung counter-regulatory renin-angiotensin system (RAS) axis, conversion of deleterious angiotensin (ANG) II to protective ANG [1-7] is predominantly mediated by proinflammatory prolyloligopeptidase (POP).
•	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.
•	A reasonable treatment strategy in COVID-19-related acute lung injury that deserves further investigation would be restoration of lung counter-regulatory RAS axis efficiency by delivering functional recombinant (r)ACE2 in the lungs that traps the virus. Additionally or alternatively, the potential benefits resulting from lowering POP activity should also be explored.