title: A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability.
abstract: 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.
authors: Philip Morris International R&D, Philip Morris Products S,A,, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. hector.deleon@pmi.com.
authors: Héctor
authors: H
authors: De León
authors: Stéphanie
authors: S
authors: Boué
authors: Walter K
authors: WK
authors: Schlage
authors: Natalia
authors: N
authors: Boukharov
authors: Jurjen W
authors: JW
authors: Westra
authors: Stephan
authors: S
authors: Gebel
authors: Aaron
authors: A
authors: VanHooser
authors: Marja
authors: M
authors: Talikka
authors: R Brett
authors: RB
authors: Fields
authors: Emilija
authors: E
authors: Veljkovic
authors: Michael J
authors: MJ
authors: Peck
authors: Carole
authors: C
authors: Mathis
authors: Vy
authors: V
authors: Hoang
authors: Carine
authors: C
authors: Poussin
authors: Renee
authors: R
authors: Deehan
authors: Katrin
authors: K
authors: Stolle
authors: Julia
authors: J
authors: Hoeng
authors: Manuel C
authors: MC
authors: Peitsch
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000473:pathology*; D001808:Blood Vessels / Q000473:pathology*; D016000:Cluster Analysis; D019992:Databases as Topic; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D051379:Mice; D008955:Models, Cardiovascular; D016017:Odds Ratio; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000473:pathology*; D015398:Signal Transduction; D012984:Software; D059467:Transcriptome / Q000235:genetics; D057170:Translational Research, Biomedical
chemical_list: D001057:Apolipoproteins E