© 1998 American Heart Association, Inc.
Rapid Communications |
Inducible Expression of Lectin-like Oxidized LDL Receptor-1 in Vascular Endothelial Cells
From the Departments of Geriatric Medicine (N.K., T. Murase, H.M., T.K.) and Pharmacology (T.A., T.S., T. Masaki), Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Correspondence to Noriaki Kume, MD, PhD, Department of Geriatric Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. E-mail nkume{at}kuhp.kyoto-u.ac.jp
Abstract—Endothelial
dysfunction, or activation, elicited by oxidized LDL (Ox-LDL) or its
lipid constituent, has been implicated in the initiation and
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 vascular endothelial cells. In this study, we
provide evidence that LOX-1 expression can be upregulated by tumor
necrosis factor-
(TNF-) and phorbol 12-myristate
13-acetate (PMA) in cultured bovine aortic endothelial
cells. TNF- and PMA upregulated LOX-1 protein and mRNA in a time-
and dose-dependent manner. Nuclear runoff assay revealed that TNF-
stimulates transcription of the LOX-1 gene. Chinese hamster ovary K1
cells stably expressing LOX-1 internalized
1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine
perchlorate (DiI)-labeled Ox-LDL but did not significantly internalize
acetylated LDL (Ac-LDL), which was effectively suppressed by
excess amounts of unlabeled Ox-LDL but not by Ac-LDL. Upregulated
expression of LOX-1 by TNF- and PMA was associated with increased
uptake of DiI-Ox-LDL that cannot be blocked by excess 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 receptor on
vascular endothelial cells may play an important role
in endothelial activation in atherogenesis.
Key Words: atherosclerosis • tumor necrosis factor- • phorbol myristate acetate • cytokine
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