Key result
SARS-CoV-2 infection may promote severe lung injury by depleting the ACE2/MAS pathway and amplifying RAAS.
Why the study?
With ACE2 identified as the receptor for SARS-CoV-2 entry, understanding its physiological cardiovascular and pulmonary functions is needed to inform therapeutic targeting.
The loss of ACE2 protective function during SARS-CoV-2 infection provides a mechanistic rationale for exploring therapies that modulate the ACE2/MAS pathway or inhibit viral entry proteases.
Supports hypothesis generation for ACE2-modulating therapies in COVID-19 lung injury; leaves open need for clinical validation.
The rapidly evolving pandemic of severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection worldwide cost many lives. The angiotensin converting enzyme-2 (ACE-2) has been identified as the receptor for the SARS-CoV-2 viral entry. As such, it is now receiving renewed attention as a potential target for anti-viral therapeutics. We review the physiological functions of ACE2 in the cardiovascular system and the lungs, and how the activation of ACE2/MAS/G protein coupled receptor contributes in reducing acute injury and inhibiting fibrogenesis of the lungs and protecting the cardiovascular system. In this perspective, we predominantly focus on the impact of SARS-CoV-2 infection on ACE2 and dysregulation of the protective effect of ACE2/MAS/G protein pathway vs. the deleterious effect of Renin/Angiotensin/Aldosterone. We discuss the potential effect of invasion of SARS-CoV-2 on the function of ACE2 and the loss of the protective effect of the ACE2/MAS pathway in alveolar epithelial cells and how this may amplify systemic deleterious effect of renin-angiotensin aldosterone system (RAS) in the host. Furthermore, we speculate the potential of exploiting the modulation of ACE2/MAS pathway as a natural protection of lung injury by modulation of ACE2/MAS axis or by developing targeted drugs to inhibit proteases required for viral entry.
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Samavati et al. (2020) conducted a review in COVID-19 (SARS-CoV-2 infection). SARS-CoV-2 infection may lead to the loss of the protective ACE2/MAS pathway, amplifying the deleterious effects of the renin-angiotensin-aldosterone system and contributing to severe lung injury.
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