Mini-Review Article

Downregulation of Membrane-bound Angiotensin Converting Enzyme 2 (ACE2) Receptor has a Pivotal Role in COVID-19 Immunopathology

Author(s): Cristina Vieira, Lucas Nery, Ludimila Martins, Luiz Jabour, Raphael Dias and Ana Cristina Simões e Silva*

Volume 22, Issue 3, 2021

Published on: 20 October, 2020

Page: [254 - 281] Pages: 28

DOI: 10.2174/1389450121666201020154033

Price: $65


Background: The Coronavirus Disease 2019 (COVID-19) is becoming the major health issue in recent human history with thousands of deaths and millions of cases worldwide. Newer research and old experience with other coronaviruses highlighted a probable underlying mechanism of disturbance of the renin-angiotensin system (RAS) that is associated with the intrinsic effects of SARS-CoV-2 infection.

Objective: In this review, we aimed to describe the intimate connections between the RAS components, the immune system and COVID-19 pathophysiology.

Methods: This non-systematic review article summarizes recent evidence on the relationship between COVID-19 and the RAS.

Results: Several studies have indicated that the downregulation of membrane-bound ACE2 may exert a key role for the impairment of immune functions and for COVID-19 patients’ outcomes. The downregulation may occur by distinct mechanisms, particularly: (1) the shedding process induced by the SARS-CoV-2 fusion pathway, which reduces the amount of membrane-bound ACE2, stimulating more shedding by the high levels of Angiotensin II; (2) the endocytosis of ACE2 receptor with the virus itself and (3) by the interferon inhibition caused by SARS-CoV-2 effects on the immune system, which leads to a reduction of ACE2 receptor expression.

Conclusion: Recent research provides evidence of a reduction of the components of the alternative RAS axis, including ACE2 and Angiotensin-(1-7). In contrast, increased levels of Angiotensin II can activate the AT1 receptor in several organs. Consequently, increased inflammation, thrombosis and angiogenesis occur in patients infected with SARS-COV-2. Attention should be paid to the interactions of the RAS and COVID-19, mainly in the context of novel vaccines and proposed medications.

Keywords: COVID-19, SARS-COV-2, RAS, downregulation, ACE2 receptor, angiotensin II, angiotensin (1-7).

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