Role of oxidized LDL/LOX-1 in the development and progression of renal disease.

凝集素样氧化LDL受体（LOX-1）首次被证实是血管内皮细胞中的氧化LDL受体，有报道称其在引起动脉粥样硬化的常见疾病模型动物的脉管系统中增强。事实上，LOX-1增加了几种与动脉粥样硬化相关的因子的表达。因此，LOX-1被认为在动脉粥样硬化的病理生理中起重要作用。我们重点研究了LOX-1在肾损害发展中的作用。结果表明，高盐Dahl盐敏感大鼠肾LOX-1表达升高，而Dahl盐敏感大鼠是众所周知的高血压肾损害模型。相比之下，自发性高血压大鼠的肾LOX-1没有增强，血压同样升高，但没有肾功能障碍。此外，在其他肾损伤模型如5/6肾切除大鼠和单侧尿道梗阻小鼠中，也刺激了肾LOX-1的表达。亚急性tnf - α刺激也可增强肾LOX-1的表达。因此，LOX-1可能在任何类型肾损害的发展中都很重要。此外，抑制肾素-血管紧张素系统和抗氧化剂的药物可以改善与LOX-1表达减少相关的肾损伤。因此，血管紧张素II和氧化应激可能通过LOX-1表达的增加而导致肾损伤的发生。

Lectin-like oxidized LDL receptor (LOX-1), which has been firstly demonstrated to be oxidized LDL receptor in vascular endothelial cells, has reported to be enhanced in vasculature of model animals of common diseases that cause atherosclerosis. In fact, LOX-1 increases the expression of several factors relevant to atherosclerosis. Thus, LOX-1 has been considered to play an important role of the pathophysiology of atherosclerosis. We focused the role of LOX-1 in the development of renal damage. We demonstrated that renal LOX-1 expression was increased in salt-loaded Dahl salt-sensitive rats, which are well-known hypertensive renal damage model. In contrast, renal LOX-1 was not enhanced in spontaneously hypertensive rats, in which blood pressure was similarly elevated without renal dysfunction. Moreover, renal LOX-1 expression was stimulated in the other renal damage models such as 5/6-nephrectomized rats and unilateral urethral obstruction mice. Subacute TNFα stimulation also enhance renal LOX-1 expression. Therefore, LOX-1 may be important in the development of any kinds of renal damage. Also, agents to inhibit the renin-angiotensin system and antioxidants ameliorated renal damage associated with reduction of LOX-1 expression. Thus, angiotensin II and oxidative stress may attribute to the development of renal damage through increase in LOX-1 expression.