PMID- 20406653
OWN - NLM
STAT- MEDLINE
DCOM- 20100628
LR  - 20211020
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 246
IP  - 1-2
DP  - 2010 Jul
TI  - Polychlorinated biphenyl-induced VCAM-1 expression is attenuated in aortic 
      endothelial cells isolated from caveolin-1 deficient mice.
PG  - 74-82
LID - 10.1016/j.taap.2010.04.009 [doi]
AB  - 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.
CI  - 2010 Elsevier Inc. All rights reserved.
FAU - Han, Sung Gu
AU  - Han SG
AD  - Molecular and Cell Nutrition Laboratory, College of Agriculture, University of 
      Kentucky, Lexington, KY 40536, USA.
FAU - Eum, Sung Yong
AU  - Eum SY
FAU - Toborek, Michal
AU  - Toborek M
FAU - Smart, Eric
AU  - Smart E
FAU - Hennig, Bernhard
AU  - Hennig B
LA  - eng
GR  - P42 ES007380/ES/NIEHS NIH HHS/United States
GR  - P42 ES007380-130002/ES/NIEHS NIH HHS/United States
GR  - P42ES007380/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100418
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Caveolin 1)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - TSH69IA9XF (3,4,5,3',4'-pentachlorobiphenyl)
RN  - Y2I6546TMI (3,4,3',4'-tetrachlorobiphenyl)
SB  - IM
MH  - Animals
MH  - Aorta
MH  - Blotting, Western
MH  - Caveolin 1/*deficiency/genetics
MH  - Cell Adhesion/drug effects
MH  - Endothelial Cells/chemistry/*drug effects/metabolism
MH  - Fluorescent Antibody Technique
MH  - Gene Expression/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout/genetics
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Monocytes/drug effects
MH  - Polychlorinated Biphenyls/*pharmacology
MH  - RNA Interference/drug effects
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Swine
MH  - Vascular Cell Adhesion Molecule-1/analysis/*biosynthesis
PMC - PMC2895770
MID - NIHMS208486
EDAT- 2010/04/22 06:00
MHDA- 2010/06/29 06:00
PMCR- 2011/07/01
CRDT- 2010/04/22 06:00
PHST- 2010/01/25 00:00 [received]
PHST- 2010/04/09 00:00 [revised]
PHST- 2010/04/12 00:00 [accepted]
PHST- 2010/04/22 06:00 [entrez]
PHST- 2010/04/22 06:00 [pubmed]
PHST- 2010/06/29 06:00 [medline]
PHST- 2011/07/01 00:00 [pmc-release]
AID - S0041-008X(10)00136-5 [pii]
AID - 10.1016/j.taap.2010.04.009 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2010 Jul;246(1-2):74-82. doi: 10.1016/j.taap.2010.04.009. 
      Epub 2010 Apr 18.