Temporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.

Vein graft failure occurs between 1 and 6 months after implantation due to obstructive intimal hyperplasia, related in part to implantation injury. The cell-specific and temporal response of the transcriptome to vein graft implantation injury was determined by transcriptional profiling of laser capt...

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Autores principales:	Manoj Bhasin, Zhen Huang, Leena Pradhan-Nabzdyk, Junaid Y Malek, Philip J LoGerfo, Mauricio Contreras, Patrick Guthrie, Eva Csizmadia, Nicholas Andersen, Olivier Kocher, Christiane Ferran, Frank W LoGerfo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0a9020cf867e494baea46e3f055ef83f
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spelling	oai:doaj.org-article:0a9020cf867e494baea46e3f055ef83f2021-11-18T07:15:21ZTemporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.1932-620310.1371/journal.pone.0039123https://doaj.org/article/0a9020cf867e494baea46e3f055ef83f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22720046/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Vein graft failure occurs between 1 and 6 months after implantation due to obstructive intimal hyperplasia, related in part to implantation injury. The cell-specific and temporal response of the transcriptome to vein graft implantation injury was determined by transcriptional profiling of laser capture microdissected endothelial cells (EC) and medial smooth muscle cells (SMC) from canine vein grafts, 2 hours (H) to 30 days (D) following surgery. Our results demonstrate a robust genomic response beginning at 2 H, peaking at 12-24 H, declining by 7 D, and resolving by 30 D. Gene ontology and pathway analyses of differentially expressed genes indicated that implantation injury affects inflammatory and immune responses, apoptosis, mitosis, and extracellular matrix reorganization in both cell types. Through backpropagation an integrated network was built, starting with genes differentially expressed at 30 D, followed by adding upstream interactive genes from each prior time-point. This identified significant enrichment of IL-6, IL-8, NF-κB, dendritic cell maturation, glucocorticoid receptor, and Triggering Receptor Expressed on Myeloid Cells (TREM-1) signaling, as well as PPARα activation pathways in graft EC and SMC. Interactive network-based analyses identified IL-6, IL-8, IL-1α, and Insulin Receptor (INSR) as focus hub genes within these pathways. Real-time PCR was used for the validation of two of these genes: IL-6 and IL-8, in addition to Collagen 11A1 (COL11A1), a cornerstone of the backpropagation. In conclusion, these results establish causality relationships clarifying the pathogenesis of vein graft implantation injury, and identifying novel targets for its prevention.Manoj BhasinZhen HuangLeena Pradhan-NabzdykJunaid Y MalekPhilip J LoGerfoMauricio ContrerasPatrick GuthrieEva CsizmadiaNicholas AndersenOlivier KocherChristiane FerranFrank W LoGerfoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39123 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Manoj Bhasin Zhen Huang Leena Pradhan-Nabzdyk Junaid Y Malek Philip J LoGerfo Mauricio Contreras Patrick Guthrie Eva Csizmadia Nicholas Andersen Olivier Kocher Christiane Ferran Frank W LoGerfo Temporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.
description	Vein graft failure occurs between 1 and 6 months after implantation due to obstructive intimal hyperplasia, related in part to implantation injury. The cell-specific and temporal response of the transcriptome to vein graft implantation injury was determined by transcriptional profiling of laser capture microdissected endothelial cells (EC) and medial smooth muscle cells (SMC) from canine vein grafts, 2 hours (H) to 30 days (D) following surgery. Our results demonstrate a robust genomic response beginning at 2 H, peaking at 12-24 H, declining by 7 D, and resolving by 30 D. Gene ontology and pathway analyses of differentially expressed genes indicated that implantation injury affects inflammatory and immune responses, apoptosis, mitosis, and extracellular matrix reorganization in both cell types. Through backpropagation an integrated network was built, starting with genes differentially expressed at 30 D, followed by adding upstream interactive genes from each prior time-point. This identified significant enrichment of IL-6, IL-8, NF-κB, dendritic cell maturation, glucocorticoid receptor, and Triggering Receptor Expressed on Myeloid Cells (TREM-1) signaling, as well as PPARα activation pathways in graft EC and SMC. Interactive network-based analyses identified IL-6, IL-8, IL-1α, and Insulin Receptor (INSR) as focus hub genes within these pathways. Real-time PCR was used for the validation of two of these genes: IL-6 and IL-8, in addition to Collagen 11A1 (COL11A1), a cornerstone of the backpropagation. In conclusion, these results establish causality relationships clarifying the pathogenesis of vein graft implantation injury, and identifying novel targets for its prevention.
format	article
author	Manoj Bhasin Zhen Huang Leena Pradhan-Nabzdyk Junaid Y Malek Philip J LoGerfo Mauricio Contreras Patrick Guthrie Eva Csizmadia Nicholas Andersen Olivier Kocher Christiane Ferran Frank W LoGerfo
author_facet	Manoj Bhasin Zhen Huang Leena Pradhan-Nabzdyk Junaid Y Malek Philip J LoGerfo Mauricio Contreras Patrick Guthrie Eva Csizmadia Nicholas Andersen Olivier Kocher Christiane Ferran Frank W LoGerfo
author_sort	Manoj Bhasin
title	Temporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.
title_short	Temporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.
title_full	Temporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.
title_fullStr	Temporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.
title_full_unstemmed	Temporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.
title_sort	temporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/0a9020cf867e494baea46e3f055ef83f
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_version_	1718423707685224448

Temporal network based analysis of cell specific vein graft transcriptome defines key pathways and hub genes in implantation injury.

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