Identification and autoregulation of receptor for OX-LDL in cultured human coronary artery endothelial cells

Although macrophages scavenge oxidatively modified low density lipoprotein (ox-LDL) via specific receptors, the uptake of ox-LDL by endothelial cells is thought to be mediated by a different receptor (LOX-1), We examined the presence of LOX-1 on cultured human coronary artery endothelial cells (HCAECs) by RT-PCR, radioligand blot, and binding assays. LOX-1 mRNA and protein were consistently identified in HCAECs, [I-125]-oX-LDL binding assay also identified high affinity binding sites for LOX-1 on HCAECs (K-D:1.71 x 10(-8) M: B-max:29.7 ng/mg protein). There was no change in LOX-1 expression in HCAECs treated with native-LDL, In contrast, incubation of HCAECs with ox-LDL (10-40 mu g/ml) increased LOX-1 expression (mRNA and protein). The upregulation of LOX-1 expression appeared to be dependent on ox-LDL concentration, Higher concentration (100 mu g/ml) however, decreased LOX-1 expression, perhaps related to its cytotoxic effect. These observations indicate that ox-LDL upregulates its own receptor on HCAECs, This phenomenon may explain enhanced uptake of ox-LDL by HCAECs in hyperlipidemia resulting in cellular dysfunction, (C) 1998 Academic Press.