The Regulation Of Proton-Sensing Lipid Receptor G2A In The Expression Of Vascular Endothelial Cell Adhesion Molecules

The expression of ICAM-1 and VCAM-1 in vascular endothelial cells, leading to monocyte adhesion to endothelial cells, and then moved to the endothelial cells and smooth muscle cell layer, and further differentiate into foam cells, foam cell formation is a major phenomenon of early stage of atherosclerosis. To study the regulation and its signaling pathways of LPC induced the expression of vascular endothelial cell adhesion molecules through G2A receptor and to clarify the mechanism of the development.of atherosclerosis, provide a theoretical basis for the treatment of atherosclerosis.LPC stimulates the expression of ICAM-1 and VCAM-1 in HUVECs, G2A receptor preferentially expressed in endothelial cells, moreover, OGR1,TDAG8 and GPR4 are expressing to some degree. And also found the expression pattern of four types of receptors that are not induced by LPC and H+. LPC promotes the expression of cell adhesion molecule without the inhibition of PTX, suggesting the signal pathway is a non PTX-sensitive pathway. Nuclear factor inhibitor (BAY) could significantly reduced the expression of ICAM-1 and VCAM-1, suggesting the transcription of ICAM-1 and VCAM-1 is regulated by the nuclear factor NFκ-B.To construct a transient expressed G2A transgenic cell clone. Stimulated with LPC the expression of ICAM-1 and VCAM-1 were increased, further demonstrated LPC (lipid ligand) stimulation of adhesion molecule ICAM-1 and VCAM-1 expression are mediated by the G2A receptor. Proton ligand of G2A (H+ or pH6.8) could inhibit the effects induced by LPC. Visible, the two ligands in the expression of adhesion molecules ICAM-1 and VCAM-1 have important regulatory role.Conclusions:G2A receptor preferentially expressed in endothelial cells, he expression pattern of four types of receptors that are not induced by LPC and H+; LPC—G2A—non PTX sensitive way—NFκ-B promotes the expression of ICAM-1; LPC—G2A—non PTX sensitive way—NFκ-B promotes the expression of VCAM-1; Proton ligand of G2A(H+ or pH6.8) could inhibit the effects induced by LPC.