HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 13/3/263    most recent 00006.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Johnson, C. D. Articles by Ramos, K. S. Search for Related Content PubMed PubMed Citation Articles by Johnson, C. D. Articles by Ramos, K. S.

Genomic profiles and predictive biological networks in oxidant-induced atherogenesis

¹ Center for Environmental and Rural Health, Texas A&M University, College Station, Texas 77843
² Department of Statistics, Texas A&M University, College Station, Texas 77843
³ National Institute of Environmental Health Sciences, Research Triangle, North Carolina 27709

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.

analysis of variance; atherosclerosis; bioinformatics; cDNA microarray; polycyclic aromatic hydrocarbons; vascular smooth muscle cells

This article has been cited by other articles:

				J. Y. King, R. Ferrara, R. Tabibiazar, J. M. Spin, M. M. Chen, A. Kuchinsky, A. Vailaya, R. Kincaid, A. Tsalenko, D. X.-F. Deng, et al. Pathway analysis of coronary atherosclerosis Physiol Genomics, September 21, 2005; 23(1): 103 - 118. [Abstract] [Full Text] [PDF]

				A. Ghazalpour, S. Doss, X. Yang, J. Aten, E. M. Toomey, A. Van Nas, S. Wang, T. A. Drake, and A. J. Lusis Thematic review series: The Pathogenesis of Atherosclerosis. Toward a biological network for atherosclerosis J. Lipid Res., October 1, 2004; 45(10): 1793 - 1805. [Abstract] [Full Text] [PDF]