ROLE OF LOX-1, A NOVEL OXIDIZED LOW-DENSITY LIPOPROTEIN RECEPTOR.IN THE PROGRESSION OF RENAL INJURY

氧化低密度脂蛋白（OxLDL）与动脉粥样硬化和肾小球硬化有关。LOX-1是最近发现的一种在血管内皮细胞中大量表达的OxLDL受体。我们以前报道过LOX-1在高血压大鼠血管中的表达明显增强。本研究的目的是研究LOX-1在高血压大鼠肾脏中的表达。Dahl盐敏感（DS）和盐耐受（DR）大鼠分别饲喂0.3%或8%NaCl饲料。一些DS 8%的大鼠用马尼地平或肼苯哒嗪处理。LOX-1基因在高血压DS 8%大鼠肾脏和肾小球中的表达明显高于正常血压DR和DS 0.3%大鼠。长期盐负荷进一步增加了DS大鼠肾脏LOX-1的表达。在DS 8%大鼠中LOX-1的上调伴随着肾脏转化生长因子-β1和I型胶原的过度表达、肾功能受损和组织学肾小球硬化改变，所有这些都被抗高血压治疗所改善。LOX-1确实在体内肾小球和体外培养的肾小球细胞中表达。另一方面，LOX-1的表达在自发性高血压大鼠的动脉中升高，但在肾脏中没有，自发性高血压大鼠表现出高血压，但肾小球硬化变化较小。总之，LOX-1在DS 8%大鼠肾脏中的上调与肾小球硬化改变和肾功能不全平行，表明肾脏LOX-1在高血压肾小球硬化进展中可能的致病作用。

Oxidized low-density lipoprotein (OxLDL) has been implicated in atherosclerosis and glomerulosclerosis. LOX-1 is a recently identified OxLDL receptor abundantly expressed in vascular endothelial cells. We previously reported that LOX-1 expression was markedly enhanced in the vasculatures of hypertensive rats. The aim of the present study was to investigate LOX-1 expression in the kidneys of hypertensive rats. Dahl salt-sensitive (DS) and salt-resistant (DR) rats were fed a 0.3% or 8% NaCl diet. Some DS 8% rats were treated with manidipine or hydralazine. LOX-1 gene expression was markedly elevated in the kidneys and glomeruli of hypertensive DS 8% rats compared with those of normotensive DR and DS 0.3% rats. Prolonged salt loading further increased the renal LOX-1 expression in DS rats. The LOX-1 upregulation in DS 8% rats was accompanied by renal overexpression of transforming growth factor-β1 and type I collagen, impaired renal function, and histological glomerulosclerotic changes, all of which were ameliorated by anti-hypertensive treatment. LOX-1 was indeed expressed in the glomeruli in vivo and in cultured glomerular cells in vitro. On the other hand, LOX-1 expression was elevated in the aortas but not the kidneys of spontaneously hypertensive rats, which exhibited hypertension but minor glomerulosclerotic changes. In conclusion, the LOX-1 upregulation in the kidney of DS 8% rats was in parallel to glomerulosclerotic changes and renal dysfunction, suggesting a possible pathogenetic role for renal LOX-1 in the progression to hypertensive glomerulosclerosis.