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

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 corona-viruses highlighted a probable underlying mechanism of disturbance of the renin-angiotensin system (RAS) that is associ-ated with 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' outcome. The downregulation may occur by distinct mecha-nisms, particularly: (1) the shedding process induced by SARS-CoV-2 fusion pathway, which reduces the amount of mem-brane-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 immune system, which leads to 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. Atten-tion should be paid to the interactions of the RAS and COVID-19, mainly in the context of novel vaccines and proposed medications.

journal_name

Curr Drug Targets

journal_title

Current drug targets

authors

Vieira C,Nery L,Martins L,Jabour L,Dias R,Simões E Silva AC

doi

10.2174/1389450121666201020154033

subject

Has Abstract

pub_date

2020-10-20 00:00:00

eissn

1389-4501

issn

1873-5592

pii

CDT-EPUB-110767

pub_type

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