Abstract
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 κB 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.
Original language | English (US) |
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Pages (from-to) | 572-580 |
Number of pages | 9 |
Journal | Circulation research |
Volume | 100 |
Issue number | 4 |
DOIs | |
State | Published - Mar 2007 |
Externally published | Yes |
Keywords
- Endothelium
- G protein-coupled receptor
- ICAM-1
- NFκB
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine