Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

New Drug Targets to Prevent Death due to Stroke: Results of Protein-Protein Interaction Network, Enrichment and Annotation Analyses.

Version 1 : Received: 2 September 2021 / Approved: 3 September 2021 / Online: 3 September 2021 (15:11:00 CEST)

How to cite: Maes, M.; Nikiforov, N.; Plaimas, K.; Suratanee, A.; Reiche, E.M. New Drug Targets to Prevent Death due to Stroke: Results of Protein-Protein Interaction Network, Enrichment and Annotation Analyses.. Preprints 2021, 2021090070 (doi: 10.20944/preprints202109.0070.v1). Maes, M.; Nikiforov, N.; Plaimas, K.; Suratanee, A.; Reiche, E.M. New Drug Targets to Prevent Death due to Stroke: Results of Protein-Protein Interaction Network, Enrichment and Annotation Analyses.. Preprints 2021, 2021090070 (doi: 10.20944/preprints202109.0070.v1).

Abstract

This study used established biomarkers of death due to ischemic stroke (IS) and performed network, enrichment, and annotation analysis. Protein-protein interaction (PPI) network analysis revealed that the backbone of the highly connective network of IS death consisted of IL6, ALB, TNF, SERPINE1, VWF, VCAM1, TGFB1, and SELE. Cluster analysis revealed immune and hemostasis subnetworks, which were strongly interconnected through the major switches ALB and VWF. Enrichment analysis revealed that the PPI immune subnetwork of death due to IS was highly associated with TLR2/4, TNF, JAK-STAT, NOD, IL10, IL13, IL4, and TGF-β1/SMAD pathways. The top biological and molecular functions and pathways enriched in the hemostasis network of death due IS were platelet degranulation and activation, the intrinsic pathway of fibrin clot formation, the urokinase-type plasminogen activator pathway, post-translational protein phosphorylation, integrin cell surface interactions, and the proteoglycan-integrin-extra cellular matrix complex (ECM). Regulation Explorer analysis of transcriptional factors shows: a) that NFKB1, RELA and SP1 were the major regulating actors of the PPI network; and b) hsa-mir-26-5p and hsa-16-5p were the major regulating microRNA actors. In conclusion, prevention of death due to IS should consider that current IS treatments may be improved by targeting VWF, VEGFA, proteoglycan-integrin-ECM complex, NFKB/RELA and SP1.

Keywords

stroke; inflammation; neuro-immune; cytokines; hemostasis; coagulation; protein-protein interactions

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