Title:Downregulation of Membrane-bound Angiotensin Converting Enzyme 2 (ACE2) Receptor has a Pivotal Role in COVID-19 Immunopathology
Volume: 22
Issue: 3
Author(s): Cristina Vieira, Lucas Nery, Ludimila Martins, Luiz Jabour, Raphael Dias and Ana Cristina Simões e Silva*
Affiliation:
- Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG,Brazil
Keywords:
COVID-19, SARS-COV-2, RAS, downregulation, ACE2 receptor, angiotensin II, angiotensin (1-7).
Abstract:
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.
