New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses

This study used established biomarkers of death from ischemic stroke (IS) versus stroke survival to perform network, enrichment, and annotation analyses. Protein-protein interaction (PPI) network analysis revealed that the backbone of the highly connective network of IS death consisted of <i>I...

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Autores principales:	Michael Maes, Nikita G. Nikiforov, Kitiporn Plaimas, Apichat Suratanee, Daniela Frizon Alfieri, Edna Maria Vissoci Reiche
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	stroke inflammation neuroimmune cytokines hemostasis coagulation Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/a20fa28ac0994623ba113f2ffe675382
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spelling	oai:doaj.org-article:a20fa28ac0994623ba113f2ffe6753822021-11-25T17:53:30ZNew Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses10.3390/ijms2222121081422-00671661-6596https://doaj.org/article/a20fa28ac0994623ba113f2ffe6753822021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12108https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067This study used established biomarkers of death from ischemic stroke (IS) versus stroke survival to perform network, enrichment, and annotation analyses. Protein-protein interaction (PPI) network analysis revealed that the backbone of the highly connective network of IS death consisted of <i>IL6</i>, <i>ALB</i>, <i>TNF</i>, <i>SERPINE1</i>, <i>VWF</i>, <i>VCAM1</i>, <i>TGFB1</i>, and <i>SELE</i>. Cluster analysis revealed immune and hemostasis subnetworks, which were strongly interconnected through the major switches <i>ALB</i> and <i>VWF</i>. Enrichment analysis revealed that the PPI immune subnetwork of death due to IS was highly associated with <i>TLR2/4</i>, <i>TNF</i>, <i>JAK-STAT</i>, <i>NOD</i>, <i>IL10</i>, <i>IL13</i>, <i>IL4</i>, and <i>TGF-β1/SMAD</i> pathways. The top biological and molecular functions and pathways enriched in the hemostasis network of death due to 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 extracellular matrix complex (ECM). Regulation Explorer analysis of transcriptional factors shows: (a) that <i>NFKB1</i>, <i>RELA</i> and <i>SP1</i> 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, the proteoglycan-integrin-ECM complex, TGF-β1/SMAD, NF-κB/RELA and SP1.Michael MaesNikita G. NikiforovKitiporn PlaimasApichat SurataneeDaniela Frizon AlfieriEdna Maria Vissoci ReicheMDPI AGarticlestrokeinflammationneuroimmunecytokineshemostasiscoagulationBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12108, p 12108 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	stroke inflammation neuroimmune cytokines hemostasis coagulation Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	stroke inflammation neuroimmune cytokines hemostasis coagulation Biology (General) QH301-705.5 Chemistry QD1-999 Michael Maes Nikita G. Nikiforov Kitiporn Plaimas Apichat Suratanee Daniela Frizon Alfieri Edna Maria Vissoci Reiche New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses
description	This study used established biomarkers of death from ischemic stroke (IS) versus stroke survival to perform network, enrichment, and annotation analyses. Protein-protein interaction (PPI) network analysis revealed that the backbone of the highly connective network of IS death consisted of <i>IL6</i>, <i>ALB</i>, <i>TNF</i>, <i>SERPINE1</i>, <i>VWF</i>, <i>VCAM1</i>, <i>TGFB1</i>, and <i>SELE</i>. Cluster analysis revealed immune and hemostasis subnetworks, which were strongly interconnected through the major switches <i>ALB</i> and <i>VWF</i>. Enrichment analysis revealed that the PPI immune subnetwork of death due to IS was highly associated with <i>TLR2/4</i>, <i>TNF</i>, <i>JAK-STAT</i>, <i>NOD</i>, <i>IL10</i>, <i>IL13</i>, <i>IL4</i>, and <i>TGF-β1/SMAD</i> pathways. The top biological and molecular functions and pathways enriched in the hemostasis network of death due to 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 extracellular matrix complex (ECM). Regulation Explorer analysis of transcriptional factors shows: (a) that <i>NFKB1</i>, <i>RELA</i> and <i>SP1</i> 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, the proteoglycan-integrin-ECM complex, TGF-β1/SMAD, NF-κB/RELA and SP1.
format	article
author	Michael Maes Nikita G. Nikiforov Kitiporn Plaimas Apichat Suratanee Daniela Frizon Alfieri Edna Maria Vissoci Reiche
author_facet	Michael Maes Nikita G. Nikiforov Kitiporn Plaimas Apichat Suratanee Daniela Frizon Alfieri Edna Maria Vissoci Reiche
author_sort	Michael Maes
title	New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses
title_short	New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses
title_full	New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses
title_fullStr	New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses
title_full_unstemmed	New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses
title_sort	new drug targets to prevent death due to stroke: a review based on results of protein-protein interaction network, enrichment, and annotation analyses
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a20fa28ac0994623ba113f2ffe675382
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New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses

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