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Identification and Autoregulation of Receptor for OX-LDL in Cultured Human Coronary Artery Endothelial Cells

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Abstract

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. [125I]-ox-LDL binding assay also identified high affinity binding sites for LOX-1 on HCAECs (KD:1.71 × 10−8M: Bmax: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 μg/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 μg/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.

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Address for correspondence and reprint requests: J. L. Mehta, MD, PhD, Department of Medicine, University of Florida College of Medicine, 1600 Archer Rd., P.O. Box 100277 JHMHC, Gainesville, FL 32610. Fax: (352) 379-4161. E-mail:[email protected].

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