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

Journal Article · Thu Jul 15 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.04.009· OSTI ID:21460188

Han, Sung Gu ^[1]; Eum, Sung Yong; Toborek, Michal ^[2]; Smart, Eric ^[3]; Hennig, Bernhard ^[1]

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1. Molecular and Cell Nutrition Laboratory, College of Agriculture, University of Kentucky, Lexington, KY 40536 (United States)
2. Department of Neurosurgery, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States)
3. Department of Pediatrics, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States)

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.

• OSTI ID: 21460188
• Journal Information: Toxicology and Applied Pharmacology, Vol. 246, Issue 1-2; Other Information: DOI: 10.1016/j.taap.2010.04.009; PII: S0041-008X(10)00136-5; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADHESION
ARTERIOSCLEROSIS
CELL MEMBRANES
ENDOTHELIUM
MICE
MONOCYTES
POLYCHLORINATED BIPHENYLS
ANIMAL TISSUES
ANIMALS
AROMATICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARDIOVASCULAR DISEASES
CELL CONSTITUENTS
CHLORINATED AROMATIC HYDROCARBONS
DISEASES
HALOGENATED AROMATIC HYDROCARBONS
LEUKOCYTES
MAMMALS
MATERIALS
MEMBRANES
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
RODENTS
VASCULAR DISEASES
VERTEBRATES