Genomic profiles and predictive biological networks in oxidant-induced atherogenesis.

نویسندگان

  • 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
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Effects of Heracleum Persicum Hydroalcoholic Extract on Insulin, Serum Anti-Oxidant Enzymes, Glucose, and Lipid Profiles in Alloxan-Induced Diabetic Rats

Background: Heracleum persicum (H. persicum) is a medicinal herb used in Iranian traditional medicine for its anti-toxic property. It is commonly consumed in the form of food additives and as a medicinal herbal tonic to treat liver and kidney diseases. The present study aimed to investigate the anti-oxidant, anti-diabetic, and anti-hyperlipidemic effects of H. persicum hydroalcoholic extract in...

متن کامل

Mitochondrial Oxidative Stress Significantly Influences Atherogenic Risk and Cytokine-Induced Oxidant Production

BACKGROUND Oxidative stress associated with cardiovascular disease (CVD) risk factors contributes to disease development. However, less is known whether specific subcellular components play a role in disease susceptibility. In this regard, it has been previously reported that vascular mitochondrial damage and dysfunction are associated with atherosclerosis. However, no studies have determined w...

متن کامل

Insight into redox-regulated gene networks in vascular cells

To understand the complex nature of the atherogenic response initiated by oxidative stress in vascular smooth muscle cells (vSMCs), computational prediction methodology was employed to define putative gene-gene and gene-environment interactions in vSMCs subjected to oxidative chemical stress. Computational relationships were derived from the global gene expression profiles of murine cells chall...

متن کامل

Protective effect of Berberis vulgaris on Fenton reaction-induced DNA cleavage

Objective: Berberis vulgaris contains antioxidants that can inhibit DNA cleavage. The purpose of this study was to evaluate the antioxidant and protective activity of B. vulgaris on DNA cleavage. <span style="font-size: medium;"...

متن کامل

Functionally defective high density lipoprotein is pro-oxidant : a deviation from normal atheroprotective character

High-density lipoprotein is a potential life saving antiatherogenic molecule. However, not all HDL is functionally similar, it can become dysfunctional and may increase atherosclerotic risk. At present, it is unknown, which structural alterations of HDL are essential accounting for its defective functionality and the precise pro-atherogenic mechanisms of action. This study is aimed at identific...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Physiological genomics

دوره 13 3  شماره 

صفحات  -

تاریخ انتشار 2003