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Am J Physiol Lung Cell Mol Physiol
. 2020 Jul 8.
doi: 10.1152/ajplung.00189.2020. Online ahead of print.
DISEQUILIBRIUM BETWEEN THE CLASSIC RENIN-ANGIOTENSIN SYSTEM AND ITS OPPOSING ARM IN SARS-COV-2 RELATED LUNG INJURY
Riccardo Sarzani 1 , Federico Giulietti 2 , Chiara Di Pentima 2 , Piero Giordano 3 , Francesco Spannella 2
Affiliations
- PMID: 32639866
- DOI: 10.1152/ajplung.00189.2020
Abstract
A dysregulation of the renin-angiotensin-system (RAS) has been involved in the genesis of lung injury and acute respiratory distress syndrome (ARDS) from different causes, including several viral infections. The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection of pneumocytes, the hallmark of the pandemic coronavirus disease 2019 (COVID-19) involving both alveolar interstitium and capillaries, is linked to angiotensin-converting-enzyme 2 (ACE2) binding and its functional downregulation. ACE2 is a key enzyme for the balance between the two main arms of the RAS: the ACE/Angiotensin (Ang) II/Ang II type 1 receptor axis ("classic RAS"), and the ACE2/Ang 1-7/MasR axis ("anti-RAS"). The ACE2 downregulation, as a result of SARS-coronaviruses binding, enhances the "classic RAS", leading to lung damage and inflammation with leaky pulmonary blood vessels and fibrosis, when the attenuation mediated by the "anti-RAS" arm is reduced. ACE inhibitors (ACE-I) and Ang II type 1 receptor blockers (ARB), effective in cardiovascular diseases, were found to prevent and counteract acute lung injury in several experimental models, by restoring the balance between these two opposing arms. The evidence of RAS arms disequilibrium in COVID-19 and the hypothesis of a beneficial role of RAS modulation supported by preclinical and clinical studies are the focus of the present review. Preclinical and clinical studies on drugs balancing RAS arms might be the right way to counter COVID-19.
Keywords: ACE2; Ace-inhibitors; COVID-19; Renin-Angiotensin-System; acute respiratory distress syndrome.