4. ACE2 is expressed in various organs and plays an important
role in organ injury secondary to COVID-19
According to the latest clinical research, the infected patients not
only have respiratory symptoms, but also have cardiovascular, digestive,
central system, renal and other symptoms(Guan et al. , 2020). ACE2
is a type Ⅰ integral membrane glycoprotein widely expressed in lung,
heart, endothelium, kidneys, gastrointestinal tract and so on(Zouet al. , 2020). Based on the findings, the organs, which highly
express ACE2, may be vulnerable to SARS-CoV-2 infection. The decrease of
ACE2 expression may accelerate lung injury because ACE2 is a protective
molecule of RAAS, which induce the inflammatory response and organ
damage. Binding to the ACE2 receptor is a critical initial step for
SARS-CoV-2 to entry into target cells. In the process of infection, it
is likely to require two kinds of transmembrane proteases: ADAM17
metalloproteinase and TMPRSS2 transmembrane protease. ACE2 could be cut
by ADAM17 metalloproteinase, which hinders the binding of virus and
ACE2(Lambert et al. , 2005); while TMPRSS2 transmembrane protease
is required to the process, assisting the combination of ACE2 and
SARS-CoV-2(Iwata-Yoshikawa et al. , 2019). SARS-CoV-2 appears not
only to gain the initial entry through ACE2 but also subsequently to
down-regulate ACE2 expression, which leads to the immune response
imbalance caused by ACE/Ang Ⅱ/AT1R activation(Vaduganathan et
al. , 2020). The down-regulation of ACE2 reduces the level of Ang (1-7),
and subsequently increases the production of Ang Ⅱ, which activates the
RAAS and enhances inflammation. (Figure 2 )