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(Circulation Research. 2007;100:572.)
© 2007 American Heart Association, Inc.

Integrative Physiology

Absence of the G Protein–Coupled Receptor G2A in Mice Promotes Monocyte/Endothelial Interactions in Aorta

David T. Bolick, Angela M. Whetzel, Marcus Skaflen, Tracy L. Deem, Jianyi Lee, Catherine C. Hedrick

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.

Correspondence to Catherine C. Hedrick, PhD, Cardiovascular Research Center, University of Virginia, PO Box 801394, 415 Lane Rd, MR5 Rm G123, Charlottesville, VA 22908. 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 E-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 • NFB • endothelium • ICAM-1

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