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Bioinformatics and system biology approach to identify the influences of COVID-19 on cardiovascular and hypertensive comorbidities

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected individuals that have hypertension or cardiovascular comorbidities have an elevated risk of serious coronavirus disease 2019 (COVID-19) disease and high rates of mortality but how COVID-$19$ and cardiovascular diseases interact are unclear. We therefore sought to identify novel mechanisms of interaction by identifying genes with altered expression in SARS-CoV-$2$ infection that are relevant to the pathogenesis of cardiovascular disease and hypertension. Some recent research shows the SARS-CoV-$2$ uses the angiotensin converting enzyme-$2$ (ACE-$2$) as a receptor to infect human susceptible cells. The ACE2 gene is expressed in many human tissues, including intestine, testis, kidneys, heart and lungs. ACE2 usually converts Angiotensin I in the renin-angiotensin-aldosterone system to Angiotensin II, which affects blood pressure levels. ACE inhibitors prescribed for cardiovascular disease and hypertension may increase the levels of ACE-$2$, although there are claims that such medications actually reduce lung injury caused by COVID-$19$. We employed bioinformatics and systematic approaches to identify such genetic links, using messenger RNA data peripheral blood cells from COVID-$19$ patients and compared them with blood samples from patients with either chronic heart failure disease or hypertensive diseases. We have also considered the immune response genes with elevated expression in COVID-$19$ to those active in cardiovascular diseases and hypertension. Differentially expressed genes (DEGs) common to COVID-$19$ and chronic heart failure, and common to COVID-$19$ and hypertension, were identified; the involvement of these common genes in the signalling pathways and ontologies studied. COVID-$19$ does not share a large number of differentially expressed genes with the conditions under consideration. However, those that were identified included genes playing roles in T cell functions, toll-like receptor pathways, cytokines, chemokines, cell stress, type 2 diabetes and gastric cancer. We also identified protein-protein interactions, gene regulatory networks and suggested drug and chemical compound interactions using the differentially expressed genes. The result of this study may help in identifying significant targets of treatment that can combat the ongoing pandemic due to SARS-CoV-$2$ infection.

Type Journal
ISBN 1477-4054 (Electronic) 1467-5463 (Linking)
Authors Nashiry, A.; Sarmin Sumi, S.; Islam, S.; Quinn, J. M. W.; Moni, M. A.
Responsible Garvan Author Dr Mohammad Ali Moni
Publisher Name BRIEFINGS IN BIOINFORMATICS
Published Date 2021-03-22
Published Volume 22
Published Issue 2
Published Pages 1387-1401
Status Published in-print
DOI 10.1093/bib/bbaa426
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/33458761