Epithelial and Endothelial Expressions of ACE2: SARS-CoV-2 Entry Routes

Angiotensin converting enzyme 2 (ACE2) is a main receptor for SARS-CoV-2 entry to the host cell. ACE2 is one of the key enzymes in renin-angiotensin system and plays a vital role in the maintenance of cardiovascular function. ACE/ACE2 balance is critical in the regulation of blood pressure, electrolyte homeostasis, vascular and cardiac remodeling and inflammation. ACE2 was shown to be abundantly present in human epithelial cells of the lung and enterocytes of the small intestine as well as in endothelial cells of the arterial and venous vessels. ACE2 and TMPRSS2 are colocalized on the cell surface and produced a critical step host cell entry of SARS-CoV-2. TMPRSS2-cleaved ACE2 permits SARS-CoV-2 host cell entry however, ADAM17-cleaved ACE2 produces protective effects in several organs. Differently, basigin (CD147) was suggested as a putative alternate receptor for SARS-CoV-2 entry into endothelial cells. The intestinal ACE2 receptor is associated with the neutral amino acid transporter B0AT1 and ACE2 is necessary for the expression of this transporter on the luminal surface of intestinal epithelial cells. There is a good association between the localization of SARS-CoV-2 binding receptor ACE2 and the disease target organs in respiratory, cardiovascular and gastrointestinal systems. Decreased expression of ACE2, being a receptor for coronavirus, would prevent cellular entry of the virus thereby reducing progression of the infection. However, increased ACE2 expression produces beneficial health effects. Further studies are needed to clarify this conflicting situation. Currently, it is recommended to continue the therapy with ACE2-increasing drugs in patients with COVID-19.