Upregulation of ACE2 Expression and its Relationship to Increased Shear Stress: A Protective Mechanism Lost in Cardiovascular Disease
Ying Gue, PhD
Kaneko N, Satta S, Komuro Y, Muthukrishnan SD, Kakarla V, Guo L, An J, Elahi F, Kornblum HI, Liebeskind DS, et al. Flow-Mediated Susceptibility and Molecular Response of Cerebral Endothelia to SARS-CoV-2 Infection. Stroke. 2020.
On March 11, 2020, the World Health Organisation (WHO) officially announced the Coronavirus Disease 2019 (COVID-19) as a pandemic. The outbreak originated in China, and. as of now, has over 3 million cases with over 200,000 deaths as a result. The disease is attributed to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
As the SARS-CoV-2 enters the host cell by binding the spike (S) protein to angiotensin converting enzyme 2 (ACE2), there has been an increased interest in studying the effect of ACE2 and the virus. Observational studies have shown that conditions which result in reduced ACE2 tissue expression will have a more severe disease course, notably males, advanced age, and patients with hypertension. Apart from the respiratory sequalae associated with COVID-19 infection, severe disease is further complicated by thromboembolic phenomenon including stroke. However, the mechanism underlying cerebral endothelial and response to COVID-19 infection remains unclear.
In this article by Kaneko et al., utilizing ex vivo models of human brain endothelial tissues, the authors were able to establish firstly, expression of ACE2 by human brain endothelial cells is low; secondly, ACE2 expression is increased in the presence of shear stress which facilitates binding of S protein of SARS-COV-2 to ACE2; and lastly, the binding triggers unique genes in human endothelial cells which are up-regulated to combat the infection.