IDENTIFICATION AND AUTOREGULATION OF RECEPTOR FOR OX-LDL IN CULTURED HUMAN CORONARY-ARTERY ENDOTHELIAL-CELLS

Although macrophages scavenge oxidatively modified low density lipopro tein (ox-LDL) via specific receptors, the uptake of ox-LDL by endothel ial cells is thought to be mediated by a different receptor (LOX-1), W e examined the presence of LOX-1 on cultured human coronary artery end othelial cells (HCAECs) by RT-PCR, radioligand blot, and binding assay s. LOX-1 mRNA and protein were consistently identified in HCAECs, [I-1 25]-oX-LDL binding assay also identified high affinity binding sites f or LOX-1 on HCAECs (K-D:1.71 x 10(-8) M: B-max:29.7 ng/mg protein). Th ere was no change in LOX-1 expression in HCAECs treated with native-LD L, In contrast, incubation of HCAECs with ox-LDL (10-40 mu g/ml) incre ased LOX-1 expression (mRNA and protein). The upregulation of LOX-1 ex pression appeared to be dependent on ox-LDL concentration, Higher conc entration (100 mu g/ml) however, decreased LOX-1 expression, perhaps r elated to its cytotoxic effect. These observations indicate that ox-LD L upregulates its own receptor on HCAECs, This phenomenon may explain enhanced uptake of ox-LDL by HCAECs in hyperlipidemia resulting in cel lular dysfunction, (C) 1998 Academic Press.