Functional characterization and expression analysis of novel alternative splicing isoforms of Olr1 gene during mouse embryogenesis

LOX-1 (Lectin-like oxidized low-density lipoprotein receptor-1) is the primary endothelial receptor of oxidized LDL (oxLDL). Both in vitro and in vivo experiments have shown this protein to be important in the initiation of atherosclerosis and to be up-regulated by pro-atherogenic factors. Recently, it has been demonstrated that Olr1, the gene encoding Lox-1, is important for tumor growth and for maintaining the transformed state in different cancer cell lines, suggesting that it acts in a molecular pathway connecting cancer and atherosclerosis. Both diseases in humans are characterized by uncontrolled regulation of cellular growth and differentiation. We present evidence that Olr1 is expressed during mouse embryogenesis in developmental stages (from 7.5 to 9.5 dpc) in which cardiogenesis occurs. In addition, we identify two novel Olr1 isoform (hereafter referred to as D3D5Olr1 and D2D5Olr1) whose spatio-temporal expression pattern overlaps with Olr1 in vivo. In vitro, D3D5Olr1 localizes to the cell surface membrane as Olr1, in contrast with D2D5Olr1; these data suggest that D2D5Olr1 isoform translates a receptor that does not reach the plasma membrane. Accordingly, in silico transmembrane protein topology prediction analyses, show that D2D5Olr1 does not contain any transmembrane region. Finally, both isoforms can activate the same genetic pathways underlying Olr1 expression, such as, hypoxia and inflammation, even if with a different efficiency. All these data suggest a new functional involvement of Olr1, and probably of its spliceforms, in murine cardiogenesis and angiogenesis.