Native low density lipoprotein. Endothelial cell recruitment of mononuclear cells.

Abstract

The effect of native low density lipoprotein (LDL) on human umbilical vein endothelial cell (EC) recruitment of mononuclear cells (Monos) was investigated. ECs were exposed to LDL at atherogenic concentrations (240 mg cholesterol [Chol]/dl) for as long as 4 days (LDL-treated ECs). LDL-treated ECs bound substantially greater amounts of freshly isolated human monocytes and U937 cells than did control ECs. The enhanced Mono binding was time and LDL concentration dependent. LDL-induced binding was reduced to control levels when cycloheximide was added together with LDL, indicating that de novo protein synthesis was required. Furthermore, this LDL effect was not a general feature of apolipoproteins, as high density lipoprotein in physiologically relevant concentrations (45 mg Chol/dl, 4 days) had no effect on EC-Mono binding. Conditioned media from LDL-treated EC cultures did not increase EC binding of Monos. In contrast, minimally modified LDL increased EC-Mono binding more than eightfold. In conclusion, LDL in concentrations associated with the premature development of atherosclerosis increased EC affinity for Monos. Such LDL-induced alterations in EC physiology likely represent a proinflammatory response and an early step in atherogenesis.