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A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability

BACKGROUND: Numerous inflammation-related pathways have been shown to play important roles in atherogenesis. Rapid and efficient assessment of the relative influence of each of those pathways is a challenge in the era of “omics” data generation. The aim of the present work was to develop a network m...

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Autores principales: De León, Héctor, Boué, Stéphanie, Schlage, Walter K, Boukharov, Natalia, Westra, Jurjen W, Gebel, Stephan, VanHooser, Aaron, Talikka, Marja, Fields, R Brett, Veljkovic, Emilija, Peck, Michael J, Mathis, Carole, Hoang, Vy, Poussin, Carine, Deehan, Renee, Stolle, Katrin, Hoeng, Julia, Peitsch, Manuel C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227037/
https://www.ncbi.nlm.nih.gov/pubmed/24965703
http://dx.doi.org/10.1186/1479-5876-12-185
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author De León, Héctor
Boué, Stéphanie
Schlage, Walter K
Boukharov, Natalia
Westra, Jurjen W
Gebel, Stephan
VanHooser, Aaron
Talikka, Marja
Fields, R Brett
Veljkovic, Emilija
Peck, Michael J
Mathis, Carole
Hoang, Vy
Poussin, Carine
Deehan, Renee
Stolle, Katrin
Hoeng, Julia
Peitsch, Manuel C
author_facet De León, Héctor
Boué, Stéphanie
Schlage, Walter K
Boukharov, Natalia
Westra, Jurjen W
Gebel, Stephan
VanHooser, Aaron
Talikka, Marja
Fields, R Brett
Veljkovic, Emilija
Peck, Michael J
Mathis, Carole
Hoang, Vy
Poussin, Carine
Deehan, Renee
Stolle, Katrin
Hoeng, Julia
Peitsch, Manuel C
author_sort De León, Héctor
collection PubMed
description BACKGROUND: Numerous inflammation-related pathways have been shown to play important roles in atherogenesis. Rapid and efficient assessment of the relative influence of each of those pathways is a challenge in the era of “omics” data generation. The aim of the present work was to develop a network model of inflammation-related molecular pathways underlying vascular disease to assess the degree of translatability of preclinical molecular data to the human clinical setting. METHODS: We constructed and evaluated the Vascular Inflammatory Processes Network (V-IPN), a model representing a collection of vascular processes modulated by inflammatory stimuli that lead to the development of atherosclerosis. RESULTS: Utilizing the V-IPN as a platform for biological discovery, we have identified key vascular processes and mechanisms captured by gene expression profiling data from four independent datasets from human endothelial cells (ECs) and human and murine intact vessels. Primary ECs in culture from multiple donors revealed a richer mapping of mechanisms identified by the V-IPN compared to an immortalized EC line. Furthermore, an evaluation of gene expression datasets from aortas of old ApoE(-/-) mice (78 weeks) and human coronary arteries with advanced atherosclerotic lesions identified significant commonalities in the two species, as well as several mechanisms specific to human arteries that are consistent with the development of unstable atherosclerotic plaques. CONCLUSIONS: We have generated a new biological network model of atherogenic processes that demonstrates the power of network analysis to advance integrative, systems biology-based knowledge of cross-species translatability, plaque development and potential mechanisms leading to plaque instability.
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spelling pubmed-42270372014-11-12 A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability De León, Héctor Boué, Stéphanie Schlage, Walter K Boukharov, Natalia Westra, Jurjen W Gebel, Stephan VanHooser, Aaron Talikka, Marja Fields, R Brett Veljkovic, Emilija Peck, Michael J Mathis, Carole Hoang, Vy Poussin, Carine Deehan, Renee Stolle, Katrin Hoeng, Julia Peitsch, Manuel C J Transl Med Methodology BACKGROUND: Numerous inflammation-related pathways have been shown to play important roles in atherogenesis. Rapid and efficient assessment of the relative influence of each of those pathways is a challenge in the era of “omics” data generation. The aim of the present work was to develop a network model of inflammation-related molecular pathways underlying vascular disease to assess the degree of translatability of preclinical molecular data to the human clinical setting. METHODS: We constructed and evaluated the Vascular Inflammatory Processes Network (V-IPN), a model representing a collection of vascular processes modulated by inflammatory stimuli that lead to the development of atherosclerosis. RESULTS: Utilizing the V-IPN as a platform for biological discovery, we have identified key vascular processes and mechanisms captured by gene expression profiling data from four independent datasets from human endothelial cells (ECs) and human and murine intact vessels. Primary ECs in culture from multiple donors revealed a richer mapping of mechanisms identified by the V-IPN compared to an immortalized EC line. Furthermore, an evaluation of gene expression datasets from aortas of old ApoE(-/-) mice (78 weeks) and human coronary arteries with advanced atherosclerotic lesions identified significant commonalities in the two species, as well as several mechanisms specific to human arteries that are consistent with the development of unstable atherosclerotic plaques. CONCLUSIONS: We have generated a new biological network model of atherogenic processes that demonstrates the power of network analysis to advance integrative, systems biology-based knowledge of cross-species translatability, plaque development and potential mechanisms leading to plaque instability. BioMed Central 2014-06-26 /pmc/articles/PMC4227037/ /pubmed/24965703 http://dx.doi.org/10.1186/1479-5876-12-185 Text en Copyright © 2014 De León et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Methodology
De León, Héctor
Boué, Stéphanie
Schlage, Walter K
Boukharov, Natalia
Westra, Jurjen W
Gebel, Stephan
VanHooser, Aaron
Talikka, Marja
Fields, R Brett
Veljkovic, Emilija
Peck, Michael J
Mathis, Carole
Hoang, Vy
Poussin, Carine
Deehan, Renee
Stolle, Katrin
Hoeng, Julia
Peitsch, Manuel C
A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability
title A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability
title_full A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability
title_fullStr A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability
title_full_unstemmed A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability
title_short A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability
title_sort vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability
topic Methodology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227037/
https://www.ncbi.nlm.nih.gov/pubmed/24965703
http://dx.doi.org/10.1186/1479-5876-12-185
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