FLUID SHEAR-STRESS TRANSCRIPTIONALLY INDUCES LECTIN-LIKE OXIDIZED LDLRECEPTOR-1 IN VASCULAR ENDOTHELIAL-CELLS

Fluid shear stress has been shown to modulate various endothelial func tions, including gene expression. In this study, we examined the effec t of fluid shear stress on the expression of lectin-like oxidized LDL receptor-1 (LOX-1), a novel receptor for atherogenic oxidized LDL in c ultured bovine aortic endothelial cells (BAECs). Exposure of BAECs to the physiological range of shear stress (1 to 15 dyne/cm(2)) upregulat ed LOX-1 protein and mRNA in a time-dependent fashion. LOX-1 mRNA leve ls peaked at 4 hours, and LOX-1 protein levels peaked at 8 hours. Inhi bition of de novo RNA synthesis by actinomycin D totally abolished she ar stress-induced LOX-1 mRNA expression. Furthermore, nuclear runoff a ssay showed that shear stress directly stimulates transcription of the LOX-1 gene. Chelation of intracellular Ca2+ with quin 2-AM completely reduced shear stress-induced LOX-1 mRNA expression; furthermore, the treatment of BAECs with ionomycin upregulated LOX-1 mRNA levels in a d ose-dependent manner. Taken together, physiological levels of fluid sh ear stress can regulate LOX-1 expression by a mechanism dependent on i ntracellular Ca2+ mobilization. Inducible expression of LOX-1 by fluid mechanics may play a role in localized expression of LOX-1 and athero sclerotic lesion formation in vivo.