Induction of the OxLDL receptor LOX-1 by endothelin-1 in human endothelialcells

In this study, we analyzed the effect of endothelin-l (ET-1) on expression of the lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 LOX- 1 and on oxLDL uptake in primary cultures of human umbilical vein endotheli al cells (HUVEC). LOX-1 mRNA was quantified by standard-calibrated competit ive RT-PCR, LOX-1 protein expression by Western analysis and endothelial ox LDL uptake using DiI-labeled oxLDL, ET-1 induces LOX-1 mRNA expression, rea ching its maximum after 1 h (160 +/- 14% of control, 100 nM ET-1, P < 0.05) . This increased ET-1-mediated LOX-1 mRNA expression could be inhibited by endothelin receptor B antagonist BQ-788. In addition, ET-1 stimulates LOX-1 protein expression and oxLDL uptake in HUVEC, The augmented oxLDL uptake b y ET-1 is mediated by endothelin receptor B, but not by protein kinases. Th ese data support a new pathophysiological mechanism how locally and systemi cally increased ET-1 levels could promote LOX-l-mediated oxLDL uptake in hu man endothelial cells and the development and progression of endothelial dy sfunction and atherosclerosis. (C) 2001 Academic Press.