tetano
Editor, Senior Moderator
Kaohsiung J Med Sci
. 2020 Jun 3.
doi: 10.1002/kjm2.12237. Online ahead of print.
Two Hits to the Renin-Angiotensin System May Play a Key Role in Severe COVID-19
Yu-Hsin Tseng[SUP] 1 [/SUP], Rei-Cheng Yang[SUP] 1 2 [/SUP], Tzong-Shi Lu[SUP] 3 [/SUP]
Affiliations
Abstract
The spike glycoprotein on the virion surface docking onto the angiotensin-converting enzyme (ACE) 2 dimer is an essential step in the process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in human cells-involves downregulation of ACE2 expression with systemic renin-angiotensin system (RAS) imbalance and promotion of multi-organ damage. In general, the RAS induces vasoconstriction, hypertension, inflammation, fibrosis, and proliferation via the ACE/Ang II/Ang II type 1 receptor (AT1R) axis and induces the opposite effects via the ACE2/Ang (1-7)/Mas axis. The RAS may be activated by chronic inflammation in hypertension, diabetes, obesity, and cancer. SARS-CoV-2 induces the ACE2 internalization and shedding, leading to the inactivation of the ACE2/Ang (1-7)/Mas axis. Therefore, we hypothesize that two hits to the RAS drives COVID-19 progression. In brief, the first hit originates from chronic inflammation activating the ACE/Ang II/AT1R axis, and the second originates from the COVID-19 infection inactivating the ACE2/Ang (1-7)/Mas axis. Moreover, the two hits to the RAS may be the primary reason for increased mortality in patients with COVID-19 who have comorbidities and may serve as a therapeutic target for COVID-19 treatment.
Keywords: coronavirus disease 2019; renin-angiotensin system); two hits.
. 2020 Jun 3.
doi: 10.1002/kjm2.12237. Online ahead of print.
Two Hits to the Renin-Angiotensin System May Play a Key Role in Severe COVID-19
Yu-Hsin Tseng[SUP] 1 [/SUP], Rei-Cheng Yang[SUP] 1 2 [/SUP], Tzong-Shi Lu[SUP] 3 [/SUP]
Affiliations
- PMID: 32492292
- DOI: 10.1002/kjm2.12237
Abstract
The spike glycoprotein on the virion surface docking onto the angiotensin-converting enzyme (ACE) 2 dimer is an essential step in the process of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in human cells-involves downregulation of ACE2 expression with systemic renin-angiotensin system (RAS) imbalance and promotion of multi-organ damage. In general, the RAS induces vasoconstriction, hypertension, inflammation, fibrosis, and proliferation via the ACE/Ang II/Ang II type 1 receptor (AT1R) axis and induces the opposite effects via the ACE2/Ang (1-7)/Mas axis. The RAS may be activated by chronic inflammation in hypertension, diabetes, obesity, and cancer. SARS-CoV-2 induces the ACE2 internalization and shedding, leading to the inactivation of the ACE2/Ang (1-7)/Mas axis. Therefore, we hypothesize that two hits to the RAS drives COVID-19 progression. In brief, the first hit originates from chronic inflammation activating the ACE/Ang II/AT1R axis, and the second originates from the COVID-19 infection inactivating the ACE2/Ang (1-7)/Mas axis. Moreover, the two hits to the RAS may be the primary reason for increased mortality in patients with COVID-19 who have comorbidities and may serve as a therapeutic target for COVID-19 treatment.
Keywords: coronavirus disease 2019; renin-angiotensin system); two hits.