| First Author | Bolick DT | Year | 2007 |
| Journal | Circ Res | Volume | 100 |
| Issue | 4 | Pages | 572-80 |
| PubMed ID | 17255525 | Mgi Jnum | J:133710 |
| Mgi Id | MGI:3783963 | Doi | 10.1161/01.RES.0000258877.57836.d2 |
| Citation | Bolick DT, et al. (2007) Absence of the G protein-coupled receptor G2A in mice promotes monocyte/endothelial interactions in aorta. Circ Res 100(4):572-80 |
| abstractText | 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 kappaB 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. |
