From the Role of Microbiota in Gut-Lung Axis to SARS-CoV-2 Pathogenesis

Figure 2

The function of two arms of renin-angiotensin-aldosterone system (RAAS) axis: the RAAS consists of two pathways including (i) ACE/Ang II/AT1R: in the pathway, Ang II which cleaved from Ang I by ACE activity, interacts with AT1R to induce vasoconstriction, inflammation, and fibrosis. (ii) ACE2-Ang1-7-MasR: in the pathway Ang 1-7 negatively regulate RAAS through promotion of vasodilation, anti-inflammatory and antifibrotic effects by interaction with MasR. Ang 1-7 are produced from cleavage of Ang II by ACE2 or metabolized of inactivated Ang 1-9 (cleaved from Ang I by ACE2) by ACE. The balance between two arms determines healthy state. In COVID-19 infection, ACE2, main receptor to SARS-CoV-2 entrance, is significantly decreased which results to inhibition of protective function of ACE2-Ang1-7-MasR arm. In opposite, the increased level of ACE2 resulted from ACEI and ARB medication in diabetic and hypertensive patients is considered as a double-edged sword which has been raised a big question: which aspects of increased ACE2 could be dominated during COVID-19 infection? increased susceptibility to viral infection or protective potential in RAAS system.