5.2. Angiotensin 2 (Ang II)
The renin-angiotensin system (RAS) plays an important role in regulating
vascular and kidney functions. In this system, angiotensin I (Ang I) is
generated by cleavage of angiotensinogen by renin, and then ACE converts
Ang I to Ang II. ACE2 functions to converse Ang II to Ang 1-7 (Figure
2). Ang II activates Ang II receptor type 1 (AT1R) and Ang II receptor
type 2 (AT2R). Activation of AT1R induces detrimental effects, such as
inflammation with release of cytokines, fibrosis, and impaired redox
balance, and vasoconstriction (Eguchi, Kawai, Scalia & Rizzo, 2018),
while activation of AT2R leads to anti-inflammatory, anti-fibrotic, and
vasodilation (D’Ardes et al., 2020). Ang II can also increase the
recruitment of immune cells to the injury sites and enhances the release
of inflammatory cytokines (Nataraj et al., 1999). Ang II may regulate
TLR4 mediated pathway by upregulating the expression of TLR4 and the
downstream pathways (Wu et al., 2009).
Ang II induced cell signaling pathway is a potential mechanism
underlying the cytokine storm caused by SARS‐CoV‐2. The binding of
S-protein of SARS‐CoV‐2 to ACE2 on the cell surface caused
downregulation of ACE2 expression. The reduced expression and activity
of ACE2 resulted in an increase in Ang II, leading to elevated
inflammatory responses (Figure 2). The Ang II regulators to balance the
Ang II double edged function might benefit COVID-19.