A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability
| Autor: | Carine Poussin, Michael J. Peck, Stephan Gebel, Marja Talikka, Aaron VanHooser, R. Brett Fields, Carole Mathis, Natalia Boukharov, Manuel C. Peitsch, Walter K. Schlage, Julia Hoeng, Jurjen W. Westra, Renée Deehan, Katrin Stolle, Stéphanie Boué, Emilija Veljkovic, Hector De Leon, Vy Hoang |
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| Jazyk: | angličtina |
| Předmět: |
Systems biology
Inflammation Biology Bioinformatics General Biochemistry Genetics and Molecular Biology Translational Research Biomedical Transcriptome Mice Apolipoproteins E Gene expression Odds Ratio medicine Animals Cluster Analysis Humans Vascular systems biology Vascular biology networks Medicine(all) Vascular disease Biochemistry Genetics and Molecular Biology(all) Models Cardiovascular Methodology Computational modeling General Medicine Atherosclerosis medicine.disease Plaque Atherosclerotic Plaque destabilization Gene expression profiling Atherosclerosis modeling Databases as Topic Blood Vessels medicine.symptom Signal transduction Neuroscience Software Biological network Signal Transduction |
| Zdroj: | Journal of Translational Medicine |
| ISSN: | 1479-5876 |
| DOI: | 10.1186/1479-5876-12-185 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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