Genomic organization and regulation of expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) gene

Lectin-like oxidized low-density lipoprotein receptor (LOX-1) is a recently identified receptor for oxidized low-density lipoprotein, one of the major atherogenic substances. Although LOX-1 was reported to be expressed abundantly in endothelial cells, including atheromatous lesions, the regulation of LOX-1 gene has not yet been clarified. In the present study, we isolated the rat LOX-1 gene and investigated the regulation of gene expression. The rat LOX-1 gene was encoded by a single copy gene spanning over 19 kilobases and consisted of eight exons. Exon boundaries correlated well with the functional domain boundaries of the receptor protein. The promoter region contained putative TATA and CAAT boxes and multiple cis-elements such as NF-kappaB, AP-1 and AP-2 sites, and a shear stress response element. Northern blot analysis revealed that LOX-1 gene expression was up-regulated 9-fold by shear stress, 21-fold by lipopolysaccharide, and 4-fold by tumor necrosis factor-alpha, in cultured vascular endothelial cells. LOX-1 was also expressed in macrophages but not in vascular smooth muscle cells. These data provide important information for elucidating the molecular mechanisms of LOX-1 gene regulation and suggest a role for LOX-1 in the pathophysiology of atherosclerotic cardiovascular disease.