BackgroundSevere acute respiratory syndrome MESHD coronavirus 2 (SARS-CoV-2) infection MESHD ( coronavirus disease MESHD 2019; COVID-19) is associated with adverse outcome in patients with cardiovascular disease MESHD (CVD).
AimTo characterize the interaction between SARS-CoV-2 and Angiotensin Converting Enzyme 2 (ACE2) functional networks with focus on CVD.
MethodsUsing bioinformatic tools, network medicine approaches and publicly available datasets, we investigated ACE2 tissue expression and described ACE2 interaction network which could be affected by SARS-CoV-2 infection MESHD. We identified top ACE2 interactors, including miRNAs which are shared regulators between the ACE2, virus- infection MESHD related proteins and heart interaction networks, using lung and nervous system networks as a reference. We also identified main SARS-CoV-2 risk groups and performed drug predictions for them.
ResultsWe found the same range of ACE2 expression confidence in respiratory and cardiovascular systems (averaging 4.48 and 4.64, respectively). Analysing the complete ACE2 interaction network, we identified 11 genes (ACE2, DPP4, ANPEP, CCL2, TFRC, MEP1A, ADAM17, FABP2, NPC1, CLEC4M, TMPRSS2) associated with virus- infection MESHD related processes. Previously described genes associated with cardiovascular risk factors DPP4, CCL2 and ANPEP were extensively connected with top regulators of ACE2 network, including ACE, INS and KNG1. Enrichment analysis revealed several disease MESHD phenotypes associated with interaction networks of ACE2, heart tissue, and virus- infection MESHD related protein, with the strongest associations with the following diseases MESHD (in decreasing rank order): obesity MESHD obesity HP, hypertensive disease MESHD, non-insulin dependent diabetes mellitus MESHD diabetes mellitus HP, congestive heart failure HP heart failure MESHD, and coronary artery disease MESHD. We described for the first time microRNAs-miR (miR-302c-5p, miR-1305, miR-587, miR-26b-5p, and mir-27a-3p), which were common regulators of the three networks: ACE2, heart tissue and virus- infection MESHD related proteins.
ConclusionOur study provides novel information regarding the complexity of signaling pathways affected by SARS-CoV-2 and proposes predictive tools as miR towards personalized diagnosis and therapy in COVID-19. Additionally, our study provides a list of miRNAs with biomarker potential in prediction of adverse outcome in patients with COVID-19 and CVD.
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