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

凝集素样氧化型低密度脂蛋白受体(LOX-1)是最早被证实存在于血管内皮细胞中的氧化型低密度脂蛋白受体，已被报道在导致动脉粥样硬化的常见疾病模型动物的血管内皮细胞中表达增强。事实上，LOX-1增加了几个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学中起重要作用。我们重点研究了LOX-1在肾损伤发生发展中的作用。我们发现盐负荷的Dahl盐敏感大鼠肾脏LOX-1表达增加，这是众所周知的高血压肾损伤模型。相反，在自发性高血压大鼠中，肾脏LOX-1并没有增强，在自发性高血压大鼠中，血压同样升高，但没有肾功能障碍。此外，在5/6肾切除大鼠和单侧尿路梗阻小鼠等其他肾损伤模型中，肾脏LOX-1的表达也被刺激。亚急性肿瘤坏死因子α刺激也可增强肾脏LOX-1的表达。因此，LOX-1可能在任何类型的肾损伤的发生发展中起重要作用。此外，抑制肾素-血管紧张素系统的药物和抗氧化剂改善了与LOX-1表达减少相关的肾脏损伤。因此，血管紧张素II和氧化应激可能通过增加LOX-1的表达而导致肾损害的发生。

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.