NATIVE LOW-DENSITY LIPOPROTEIN-INDUCED CALCIUM TRANSIENTS TRIGGER VCAM-1 AND E-SELECTIN EXPRESSION IN CULTURED HUMAN VASCULAR ENDOTHELIAL-CELLS

Low density lipoprotein (LDL) interactions with the endothelium are th ought to play a major role in the development of atherosclerosis. The mechanism(s) involved are not fully understood, although several Lines of evidence support the idea that oxidation of LDL increases its athe rogenicity, In this study we report for the first time that native LDL (n-LDL) binding to the LDL receptor (100-700 mu g/ml) triggers a rise in intracellular calcium which acts as a second messenger to induce v ascular cell adhesion molecule-1 (VCAM-1) expression in human coronary artery (HCAEC) and pig aortic endothelial cells (PAEC) and VCAM-1 and E-selectin expression in human aortic (HAEC) endothelial cells, Prein cubation of HCAEC with a monoclonal antibody (IgGC7) to the classical LDL receptor or pretreatment with pertussis toxin blocked the n-LDL-in duced calcium transients. Preincubation of each of the endothelial cel l lines;vith the calcium chelator -2-bis(o-aminophenoxy)ethane-N,N,N', N'-tetraacetic acetomethyl ester (BAPTA/AM) prevented the expression o f VCAM-1 and E-selectin. The increase in VCAM-1 by n-LDL results in in creased monocyte binding to HCAEC which can be attenuated by inhibitin g the intracellular calcium rise or by blocking the VCAM-1 binding sit es, These studies in human and pig endothelial cells link calcium sign aling conferred by n-LDL to mechanisms controlling the expression of E ndothelial cell adhesion molecules involved in atherogenesis.