Expression of LOX-1, an oxidized low-density lipoprotein receptor, in experimental hypertensive glomerulosclerosis
Expression of LOX-1, an oxidized low-density lipoprotein receptor, in experimental hypertensive glomerulosclerosis
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DOI：
10.1681/asn.v11101826
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发表时间：
2000-10-01
影响因子：
13.6
通讯作者：
Fujita, T
中科院分区：
文献类型：
--
作者：
Nagase, M;Kaname, S;Fujita, T
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是最近鉴定的OxLDL受体，其在血管内皮细胞中大量表达。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。LOX-1在DS 8%大鼠中的上调伴随着肾脏转化生长因子-β 1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，所有这些都通过抗高血压治疗得到改善。LOX-1确实在体内肾小球和体外培养的肾小球细胞中表达。然而，LOX-1的表达在自发性高血压大鼠的主动脉中升高，但在肾脏中没有，自发性高血压大鼠表现出高血压，但肾小球硬化轻微变化。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 that is abundantly expressed in vascular endothelial cells. 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-beta 1 and type I collagen, impaired renal function, and histologic glomerulosclerotic changes, all of which were ameliorated by antihypertensive treatment. LOX-1 was indeed expressed in the glomeruli in vivo and in cultured glomerular cells in vitro. However, LOX-1 expression was elevated in the aorta 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 parallel to glomerulosclerotic changes and renal dysfunction, suggesting a possible pathogenetic role for renal LOX-1 in the progression to hypertensive glomerulosclerosis.