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Disequilibrium between the classic renin-angiotensin system and its opposing arm in SARS-CoV-2-related lung injury.
Am J Physiol Lung Cell Mol Physiol. 2020 Aug 01; 319(2):L325-L336.AJ

Abstract

A dysregulation of the renin-angiotensin system (RAS) has been involved in the genesis of lung injury and acute respiratory distress syndrome 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)/Mas receptor (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 arm 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.

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Authors+Show Affiliations

Sarzani R
Internal Medicine and Geriatrics, "Hypertension Excellence Centre" of the European Society of Hypertension, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Ricovero e Cura per Anziani, Ancona, Italy. Department of Clinical and Molecular Sciences, University "Politecnica delle Marche," Ancona, Italy.
Giulietti F
Internal Medicine and Geriatrics, "Hypertension Excellence Centre" of the European Society of Hypertension, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Ricovero e Cura per Anziani, Ancona, Italy. Department of Clinical and Molecular Sciences, University "Politecnica delle Marche," Ancona, Italy.
Di Pentima C
Internal Medicine and Geriatrics, "Hypertension Excellence Centre" of the European Society of Hypertension, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Ricovero e Cura per Anziani, Ancona, Italy. Department of Clinical and Molecular Sciences, University "Politecnica delle Marche," Ancona, Italy.
Giordano P
Internal Medicine and Geriatrics, "Hypertension Excellence Centre" of the European Society of Hypertension, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Ricovero e Cura per Anziani, Ancona, Italy.
Spannella F
Internal Medicine and Geriatrics, "Hypertension Excellence Centre" of the European Society of Hypertension, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Nazionale Ricovero e Cura per Anziani, Ancona, Italy. Department of Clinical and Molecular Sciences, University "Politecnica delle Marche," Ancona, Italy.

MeSH

Alveolar Epithelial CellsAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme 2Angiotensin-Converting Enzyme InhibitorsBetacoronavirusCOVID-19Coronavirus InfectionsDown-RegulationHumansLung InjuryPandemicsPeptidyl-Dipeptidase APneumonia, ViralProto-Oncogene MasPulmonary AlveoliReceptors, AngiotensinRenin-Angiotensin SystemRespiratory Distress SyndromeSARS-CoV-2

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32639866

Citation

Sarzani, Riccardo, et al. "Disequilibrium Between the Classic Renin-angiotensin System and Its Opposing Arm in SARS-CoV-2-related Lung Injury." American Journal of Physiology. Lung Cellular and Molecular Physiology, vol. 319, no. 2, 2020, pp. L325-L336.
Sarzani R, Giulietti F, Di Pentima C, et al. Disequilibrium between the classic renin-angiotensin system and its opposing arm in SARS-CoV-2-related lung injury. Am J Physiol Lung Cell Mol Physiol. 2020;319(2):L325-L336.
Sarzani, R., Giulietti, F., Di Pentima, C., Giordano, P., & Spannella, F. (2020). Disequilibrium between the classic renin-angiotensin system and its opposing arm in SARS-CoV-2-related lung injury. American Journal of Physiology. Lung Cellular and Molecular Physiology, 319(2), L325-L336. https://doi.org/10.1152/ajplung.00189.2020
Sarzani R, et al. Disequilibrium Between the Classic Renin-angiotensin System and Its Opposing Arm in SARS-CoV-2-related Lung Injury. Am J Physiol Lung Cell Mol Physiol. 2020 Aug 1;319(2):L325-L336. PubMed PMID: 32639866.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Disequilibrium between the classic renin-angiotensin system and its opposing arm in SARS-CoV-2-related lung injury. AU - Sarzani,Riccardo, AU - Giulietti,Federico, AU - Di Pentima,Chiara, AU - Giordano,Piero, AU - Spannella,Francesco, Y1 - 2020/07/08/ PY - 2020/7/9/pubmed PY - 2020/8/18/medline PY - 2020/7/9/entrez KW - ACE2 KW - COVID-19 KW - SARS-CoV-2 KW - acute respiratory distress syndrome KW - renin-angiotensin system SP - L325 EP - L336 JF - American journal of physiology. Lung cellular and molecular physiology JO - Am J Physiol Lung Cell Mol Physiol VL - 319 IS - 2 N2 - A dysregulation of the renin-angiotensin system (RAS) has been involved in the genesis of lung injury and acute respiratory distress syndrome 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)/Mas receptor (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 arm 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. SN - 1522-1504 UR - https://www.unboundmedicine.com/medline/citation/32639866/Disequilibrium_between_the_classic_renin_angiotensin_system_and_its_opposing_arm_in_SARS_CoV_2_related_lung_injury_ DB - PRIME DP - Unbound Medicine ER -