Gene expression profile of endothelial cells exposed to estrogenic environmental compounds: implications to pulmonary vascular lesions

Life Sci. 2010 Jun 19;86(25-26):919-27. doi: 10.1016/j.lfs.2010.04.007. Epub 2010 Apr 21.


Aims: The cardiovascular system is an important target of estrogenic compounds. Considering the recent studies that question previously reported cardio-protective effects of estrogen, there is a growing concern that estrogenic environmental compounds may contribute to the pathology of vascular lesion formation.

Main methods: Real-time quantitative PCR was used to monitor the expression of genes involved in vascularization. Using Bayesian network modeling, we determined a gene network that estrogenic chemicals modulate in human vascular endothelial cells.

Key findings: We showed that planar and coplanar polychlorinated biphenyls (PCBs) induce the expression of different genes compared to estradiol. Non-planar PCB congener 153 induced NOTCH3 which is a new finding as well as CCL2 and IL8 similar to what has been reported by other non-planar PCBs in endothelial cells. Our gene network indicated that experimental treatments signal a network containing TGF-beta receptor and NOTCH3; molecules biologically relevant to signaling pulmonary vascular lesions.

Significance: We report in the present study that exposure of vascular endothelial cells to environmentally relevant concentrations of estrogenic PCBs induce gene networks implicated in the process of inflammation and adhesion. Our data suggest that PCBs can promote vascular lesion formation by activating gene networks involved in endothelial cell adhesion, cell growth, and pro-inflammatory molecules which were different from natural estrogen. Since inflammation and adhesion are a hallmark in the pathology of endothelial cell dysfunction, reconstructing gene networks provide insight into the potential mechanisms that may contribute to the vascular risks associated with estrogenic environmental chemicals.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bayes Theorem
  • Cell Line
  • Cluster Analysis
  • Down-Regulation / drug effects
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Environmental Exposure / analysis*
  • Environmental Pollutants / toxicity*
  • Estrogens / toxicity*
  • Gene Expression Profiling*
  • Gene Regulatory Networks / genetics
  • Humans
  • Lung / blood supply*
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology*
  • Microvessels / drug effects
  • Microvessels / metabolism
  • Microvessels / pathology
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Polymerase Chain Reaction
  • Up-Regulation / drug effects


  • Environmental Pollutants
  • Estrogens