Question

The renin-angiotensin system (RAS) is a signalling pathway that acts as a homeostatic regulator of vascular function. Its systemic actions include the regulation of blood pressure, natriuresis, and blood volume control. ACE2 is a type 1 integral membrane glycoprotein, that is expressed and active in most tissues. The highest expression of ACE2 is observed in the kidney, the endothelium, the lungs, and in the heart. ACE2 is the angiotensin-converting enzyme II.

It has been reported that ACE2 is the main host cell receptor of 2019-nCoV. It plays a crucial role in the entry of the virus into the cell to cause the final infection.

One study (*) reports the ACE2 expressed on the mucosa of oral cavity. They analyzed RNA-seq profiling data of 13 organ types with para-carcinoma normal tissues from TCGA, 14 organ types with normal tissues from FANTOM5 CAGE, and single-cell transcriptomes from independent data. They concluded that the oral cavity could be a potentially high risk for 2019-nCoV infectious.

TCGA - The Cancer Genome Atlas

FANTOM5 CAGE - The Mammalian Genome Cap Analysis of Gene Expression

(*) Xu, H., Zhong, L., Deng, J. et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci 12, 8 (2020). https://doi.org/10.1038/s41368-020-0074-x

Question: How can you design a project to study a mechanism of RAS upregulation by 2019-nCoV?

Hint: You can choose one problem (for example, blood pressure). Why are patients with high blood pressure more susceptible to 2019-nCoV infection? How can you study the upregulation of the RAS pathway?

Answer 1

ACE2

Angiotensin Converting Enzyme 2 is aglycoprotein structure act as enzyme in order to convert Angiotensin I (1-10) to Angiotensin II (1-9)/(1-7). But unfortunately this ACE2 acts as apotential receptor for cell entry of SARS-CoVs.

So if any patient having High Blood Pressure, then they shoul must express more ACE2 receptors than any normal Individual with a controlled blood pressure level.

As the HIGH BP patient express more ACE2, according to this point of view they are more susceptible to SARS-CoV-2 than normal individual.

As the digram shows we can say that all these events mainly controlled by RENIN.

So we can say that RAS upregulation may make the individual more susceptible towards the COVID-19 disease.

In order to set-up a project regarding CPVID-19 AND RAS Pathway

1 We can take two model one with normal BP and other with high BP. Then we infect them with SARS-CoV-2 at a same time with similar exposure, whose result can lead us towards the conclusion that, if High BP patient s are more susceptible to COVID-19 or not.

2. We can also As far as my knowlwdge there is no RAS upregulation after infection of COVID-019 due to ACE2 receptor expression. RAS may get upregulate due to hyper activity of innate immunity which can subsequenly lead to low volume in the blood vessel due to inflammation at infection place. As blood vol. get decrease that may activate JGA to secrete more RENIN. Then RENIN carry out further process including higher expression of ACE2.