INDUCIBLE EXPRESSION OF LECTIN-LIKE OXIDIZED LDL RECEPTOR-1 IN VASCULAR ENDOTHELIAL-CELLS

Endothelial dysfunction, or activation, elicited by oxidized LDL (Ox-L DL) or its lipid constituent, has been implicated in the initiation an d progression of atherosclerosis. We have recently identified a C-type lectin-like molecule, designated lectin-like Ox-LDL receptor-1 (LOX-1 ), which acts as a cell-surface receptor for Ox-LDL in cultured vascul ar endothelial cells. In this study, we provide evidence that LOX-1 ex pression can be upregulated by tumor necrosis factor-alpha (TNF-alpha) and phorbol 12-myristate 13-acetate (PMA) in cultured bovine aortic e ndothelial cells. TNF-alpha and PMA upregulated LOX-1 protein and mRNA in a time- and dose-dependent manner. Nuclear runoff assay revealed t hat TNF-alpha stimulates transcription of the LOX-1 gene. Chinese hams ter ovary K1 cells stably expressing LOX-1 internalized -dioctadecyl-3 ,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled Ox-LDL but did not significantly internalize acetylated LDL (Ac-LDL), which w as effectively suppressed by excess amounts of unlabeled Ox-LDL but no t by Ac-LDL. Upregulated expression of LOX-1 by TNF-a and PMA was asso ciated with increased uptake of DiI-Ox-LDL that cannot be blocked by e xcess amounts of unlabeled Ac-LDL. Taken together, LOX-1 is a receptor specific for Ox-LDL, and enhanced uptake of Ox-LDL via this novel rec eptor on vascular endothelial cells may play an important role in endo thelial activation in atherogenesis.