Published online before print January 25, 2007, doi: 10.1161/01.RES.0000258877.57836.d2
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Submitted on July 29, 2006
Revised on January 5, 2007
Accepted on January 12, 2007
Absence of the G Protein-Coupled Receptor G2A In Mice Promotes Monocyte/Endothelial Interactions in Aorta
David T. Bolick ;
From the Robert M. Berne Cardiovascular Research Center (D.T.B., A.M.W., M.S., T.D., J.L., C.C.H.), Division of Cardiovascular Medicine (C.C.H.), and Department of Pharmacology (C.C.H.), University of Virginia, Charlottesville.
* To whom correspondence should be addressed. E-mail: cch6n{at}virginia.edu.
The G protein-coupled receptor G2A is highly expressed on macrophages and lymphocytes and has been localized to atherosclerotic plaques. We examined the role of G2A in modulating monocyte/endothelial interactions in the vessel wall. We measured adhesion of WEHI 78/24 monocytes to aortas of C57BL/6 (B6) and G2A-deficient (G2A-/-) mice using an ex vivo adhesion assay. G2A-/- mice had 10-fold elevations in adhesion of monocytes to aortas. Injection of GFP-expressing wild-type macrophages into B6 and G2A-/- mice in vivo showed increased macrophage accumulation in the aortic wall of G2A-/- mice. We isolated aortic endothelial cells (ECs) from B6 and G2A-/- mice and found a 2-fold increase in intercellular adhesion molecule-1 and endothelial selectin surface expression on G2A-/- ECs using flow cytometry. Using ELISA, we found a 3-fold increase in interleukin-6 and monocyte chemoattractant protein-1 production by G2A-/- ECs compared with B6 ECs. We found a dramatic increase in nuclear localization of the p65 subunit of nuclear factor 
B in G2A-/- ECs. Transfection of G2A into G2A-/- ECs to restore normal expression levels reduced p65 nuclear localization to 35%. Restoration of G2A expression in G2A-/- ECs significantly reduced intercellular adhesion molecule-1 and endothelial selectin surface expression and reduced monocyte chemoattractant protein-1 and interleukin-6 production. Restoring G2A to G2A-/- ECs reduced monocyte adhesion by 80% compared with G2A-/- ECs in a flow chamber assay. Absence of G2A in endothelium results in proinflammatory signaling and increased monocyte/endothelial interactions in the aortic wall. Thus, endothelial G2A expression may aid in prevention of vascular inflammation and atherosclerosis.
Key words: G protein-coupled receptor • NF
B •
endothelium •
ICAM-1
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