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

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-regulatedmore » 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.« less

Authors:
 [1]; ;  [2];  [3];  [1]
  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)
Publication Date:
OSTI Identifier:
21460188
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 246; Journal 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.; Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
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

Citation Formats

Han, Sung Gu, Eum, Sung Yong, Toborek, Michal, Smart, Eric, and Hennig, Bernhard. Polychlorinated biphenyl-induced VCAM-1 expression is attenuated in aortic endothelial cells isolated from caveolin-1 deficient mice. United States: N. p., 2010. Web. doi:10.1016/j.taap.2010.04.009.
Han, Sung Gu, Eum, Sung Yong, Toborek, Michal, Smart, Eric, & Hennig, Bernhard. Polychlorinated biphenyl-induced VCAM-1 expression is attenuated in aortic endothelial cells isolated from caveolin-1 deficient mice. United States. https://doi.org/10.1016/j.taap.2010.04.009
Han, Sung Gu, Eum, Sung Yong, Toborek, Michal, Smart, Eric, and Hennig, Bernhard. 2010. "Polychlorinated biphenyl-induced VCAM-1 expression is attenuated in aortic endothelial cells isolated from caveolin-1 deficient mice". United States. https://doi.org/10.1016/j.taap.2010.04.009.
@article{osti_21460188,
title = {Polychlorinated biphenyl-induced VCAM-1 expression is attenuated in aortic endothelial cells isolated from caveolin-1 deficient mice},
author = {Han, Sung Gu and Eum, Sung Yong and Toborek, Michal and Smart, Eric and Hennig, Bernhard},
abstractNote = {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.},
doi = {10.1016/j.taap.2010.04.009},
url = {https://www.osti.gov/biblio/21460188}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1-2,
volume = 246,
place = {United States},
year = {Thu Jul 15 00:00:00 EDT 2010},
month = {Thu Jul 15 00:00:00 EDT 2010}
}