Cargando…

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 IL6, ALB,...

Descripción completa

Detalles Bibliográficos
Autores principales: Maes, Michael, Nikiforov, Nikita G., Plaimas, Kitiporn, Suratanee, Apichat, Alfieri, Daniela Frizon, Vissoci Reiche, Edna Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619767/
https://www.ncbi.nlm.nih.gov/pubmed/34829993
http://dx.doi.org/10.3390/ijms222212108
_version_ 1784605069584367616
author Maes, Michael
Nikiforov, Nikita G.
Plaimas, Kitiporn
Suratanee, Apichat
Alfieri, Daniela Frizon
Vissoci Reiche, Edna Maria
author_facet Maes, Michael
Nikiforov, Nikita G.
Plaimas, Kitiporn
Suratanee, Apichat
Alfieri, Daniela Frizon
Vissoci Reiche, Edna Maria
author_sort Maes, Michael
collection PubMed
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 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 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 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, the proteoglycan-integrin-ECM complex, TGF-β1/SMAD, NF-κB/RELA and SP1.
format Online
Article
Text
id pubmed-8619767
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-86197672021-11-27 New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses Maes, Michael Nikiforov, Nikita G. Plaimas, Kitiporn Suratanee, Apichat Alfieri, Daniela Frizon Vissoci Reiche, Edna Maria Int J Mol Sci Review 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 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 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 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, the proteoglycan-integrin-ECM complex, TGF-β1/SMAD, NF-κB/RELA and SP1. MDPI 2021-11-09 /pmc/articles/PMC8619767/ /pubmed/34829993 http://dx.doi.org/10.3390/ijms222212108 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Maes, Michael
Nikiforov, Nikita G.
Plaimas, Kitiporn
Suratanee, Apichat
Alfieri, Daniela Frizon
Vissoci Reiche, Edna Maria
New Drug Targets to Prevent Death Due to Stroke: A Review Based on Results of Protein-Protein Interaction Network, Enrichment, and Annotation Analyses
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_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_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_sort new drug targets to prevent death due to stroke: a review based on results of protein-protein interaction network, enrichment, and annotation analyses
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619767/
https://www.ncbi.nlm.nih.gov/pubmed/34829993
http://dx.doi.org/10.3390/ijms222212108
work_keys_str_mv AT maesmichael newdrugtargetstopreventdeathduetostrokeareviewbasedonresultsofproteinproteininteractionnetworkenrichmentandannotationanalyses
AT nikiforovnikitag newdrugtargetstopreventdeathduetostrokeareviewbasedonresultsofproteinproteininteractionnetworkenrichmentandannotationanalyses
AT plaimaskitiporn newdrugtargetstopreventdeathduetostrokeareviewbasedonresultsofproteinproteininteractionnetworkenrichmentandannotationanalyses
AT surataneeapichat newdrugtargetstopreventdeathduetostrokeareviewbasedonresultsofproteinproteininteractionnetworkenrichmentandannotationanalyses
AT alfieridanielafrizon newdrugtargetstopreventdeathduetostrokeareviewbasedonresultsofproteinproteininteractionnetworkenrichmentandannotationanalyses
AT vissocireicheednamaria newdrugtargetstopreventdeathduetostrokeareviewbasedonresultsofproteinproteininteractionnetworkenrichmentandannotationanalyses