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

Journal of Translational Medicine

Manuel C Peitsch³  Julia Hoeng³  Katrin Stolle³  Renee Deehan¹  Carine Poussin³  Vy Hoang¹  Carole Mathis³  Michael J Peck³  Emilija Veljkovic³  R Brett Fields¹  Marja Talikka³  Aaron VanHooser¹  Stephan Gebel²  Jurjen W Westra¹  Natalia Boukharov¹  Walter K Schlage²  Stéphanie Boué³  Héctor De León³ 

[1] Selventa, One Alewife Center, Cambridge, MA 02140, USA;Philip Morris International R&D, Philip Morris Research Laboratories GmbH, Fuggerstr.3, 51149 Koeln, Germany;Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland

关键词: Atherosclerosis modeling;    Computational modeling;    Vascular biology networks;    Plaque destabilization;    Vascular systems biology;   

Others  :  1148786
DOI  :  10.1186/1479-5876-12-185

 received in 2014-02-28, accepted in 2014-06-09,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 De León et al.; licensee BioMed Central Ltd.

【 图 表 】

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