Genomic profiles and predictive biological networks in oxidant-induced atherogenesis

C. D. Johnson, Y. Balagurunathan, K. P. Lu, M. Tadesse, M. H. Falahatpisheh, R. J. Carroll, E. R. Dougherty, C. A. Afshari, K. S. Ramos

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Atherogenic stimuli trigger complex responses in vascular smooth muscle cells (VSMCs) that culminate in activation/repression of overlapping signal transduction cascades involving oxidative stress. In the case of benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon present in tobacco smoke, the atherogenic response involves interference with redox homeostasis by oxidative intermediates of BaP metabolism. The present studies were conducted to define genomic profiles and predictive gene biological networks associated with the atherogenic response of murine (aortic) VSMCs to BaP. A combined oxidant-antioxidant treatment regimen was used to identify redox-sensitive targets during the early course of the atherogenic response. Gene expression profiles were defined using cDNA microarrays coupled to analysis of variance and several clustering methodologies. A predictor algorithm was then applied to gain insight into critical gene-gene interactions during atherogenesis. Supervised and nonsupervised analyses identified clones highly regulated by BaP, unaffected by antioxidant, and neutralized by combined chemical treatments. Lymphocyte antigen-6 complex, histocompatibility class I component factors, secreted phosphoprotein, and several interferon-inducible proteins were identified as novel redox-regulated targets of BaP. Predictor analysis confirmed these relationships and identified immune-related genes as critical molecular targets of BaP. Redox-dependent patterns of gene deregulation indicate that oxidative stress plays a prominent role during the early stages of BaP-induced atherogenesis.

Original languageEnglish (US)
Pages (from-to)263-275
Number of pages13
JournalPhysiological Genomics
Volume13
DOIs
StatePublished - Jul 2003
Externally publishedYes

Keywords

  • Analysis of variance
  • Atherosclerosis
  • Bioinformatics
  • Polycyclic aromatic hydrocarbons
  • Vascular smooth muscle cells
  • cDNA microarray

ASJC Scopus subject areas

  • Physiology
  • Genetics

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    Johnson, C. D., Balagurunathan, Y., Lu, K. P., Tadesse, M., Falahatpisheh, M. H., Carroll, R. J., Dougherty, E. R., Afshari, C. A., & Ramos, K. S. (2003). Genomic profiles and predictive biological networks in oxidant-induced atherogenesis. Physiological Genomics, 13, 263-275. https://doi.org/10.1152/physiolgenomics.00006.2003