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PMID: 20406653 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Polychlorinated biphenyl-induced VCAM-1 expression is attenuated in aortic endothelial cells isolated from caveolin-1 deficient mice.

Toxicology and applied pharmacology ·Vol. 246 ·No. 1-2 ·2010-07-00 ·Pages 74-82

Han SG, Eum SY, Toborek M, Smart E, Hennig B

Abstract

Exposure to environmental contaminants, such as polychlorinated biphenyls (PCBs), is a risk factor for the development of cardiovascular diseases such as atherosclerosis. Vascular cell adhesion molecule-1 (VCAM-1) is a critical mediator for adhesion and uptake of monocytes across the endothelium in the early stages of atherosclerosis development. The upregulation of VCAM-1 by PCBs may be dependent on functional membrane domains called caveolae. Caveolae are particularly abundant in endothelial cell membranes and involved in trafficking and signal transduction. The objective of this study was to investigate the role of caveolae in PCB-induced endothelial cell dysfunction. Primary mouse aortic endothelial cells (MAECs) isolated from caveolin-1-deficient mice and background C57BL/6 mice were treated with coplanar PCBs, such as PCB77 and PCB126. In addition, siRNA gene silencing technique was used to knockdown caveolin-1 in porcine vascular endothelial cells. In MAECs with functional caveolae, VCAM-1 protein levels were increased after exposure to both coplanar PCBs, whereas expression levels of VCAM-1 were not significantly altered in cells deficient of caveolin-1. Furthermore, PCB-induced monocyte adhesion was attenuated in caveolin-1-deficient MAECs. Similarly, siRNA silencing of caveolin-1 in porcine endothelial cells confirmed the caveolin-1-dependent VCAM-1 expression. Treatment of cells with PCB77 and PCB126 resulted in phosphorylation of extracellular signal-regulated kinase-1/2 (ERK1/2), and pharmacological inhibition of ERK1/2 diminished the observed PCB-induced increase in monocyte adhesion. These findings suggest that coplanar PCBs induce adhesion molecule expression, such as VCAM-1, in endothelial cells, and that this response is regulated by caveolin-1 and functional caveolae. Our data demonstrate a critical role of functional caveolae in the activation and dysfunction of endothelial cells by coplanar PCBs.

MeSH Terms
Animals Aorta Blotting, Western Caveolin 1/deficiency,genetics Cell Adhesion/drug effects Endothelial Cells/chemistry,drug effects,metabolism Fluorescent Antibody Technique Gene Expression/drug effects Mice Mice, Inbred C57BL Mice, Knockout/genetics Mitogen-Activated Protein Kinase 1/metabolism Mitogen-Activated Protein Kinase 3/metabolism Monocytes/drug effects Polychlorinated Biphenyls/pharmacology RNA Interference/drug effects Reverse Transcriptase Polymerase Chain Reaction Swine Vascular Cell Adhesion Molecule-1/analysis,biosynthesis
Chemicals
Caveolin 1 Vascular Cell Adhesion Molecule-1 Polychlorinated Biphenyls Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 3,4,5,3',4'-pentachlorobiphenyl 3,4,3',4'-tetrachlorobiphenyl
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Han Sung Gu
Molecular and Cell Nutrition Laboratory, College of Agriculture, University of Kentucky, Lexington, KY 40536, USA.
Eum Sung Yong
Toborek Michal
Smart Eric
Hennig Bernhard
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Article Info
Journal
Toxicology and applied pharmacology
Abbr.
Toxicol Appl Pharmacol
ISSN
1096-0333
DOI
10.1016/j.taap.2010.04.009
Published
2010-07-00
Epub
2010-00-18
Pages
74-82
Language
English
Region
United States
NLM ID
0416575
PMCID
PMC2895770
Subset
IM
Grants
NIEHS NIH HHS · P42 ES007380 · United States
NIEHS NIH HHS · P42 ES007380-130002 · United States
NIEHS NIH HHS · P42ES007380 · United States
External Links
PubMed source DOI: 10.1016/j.taap.2010.04.009 PMC Full Text View journal details
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