Chen Xiu-Ping, Zhang Tian-Tai, Du Guan-Hua
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Cardiovasc Drug Rev. 2007 Summer;25(2):146-61. doi: 10.1111/j.1527-3466.2007.00009.x.
Endothelial activation and dysfunction induced by oxidized modified low-density lipoprotein (ox-LDL) is one of the key steps in the initiation of atherosclerosis. Recent studies have shown that a new lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) mediates the recognition and internalization of ox-LDL. LOX-1 is the main receptor for ox-LDL and may play an important role in the pathogenesis of hypertension, diabetes, and, especially, of atherosclerosis. The potential role of LOX-1 in the pathogenesis of atherosclerosis includes: endocytosis of ox-LDL, expression co-location with atherosclerosis enhanced by atherosclerosis-related risk factors, elevated LOX-1 protein in cardiovascular disease, effects related to atherosclerosis and eliminated by antiatherosclerotic drugs. Identification and regulation of LOX-1 and understanding its signal transduction pathways might improve our insight toward the pathogenesis of atherosclerosis and provide a selective treatment approach. LOX-1 might be a potential and promising target for the development of novel antiatherosclerotic drugs. However, due to limited knowledge about LOX-1, there are still many questions to be answered.
氧化修饰低密度脂蛋白(ox-LDL)诱导的内皮激活和功能障碍是动脉粥样硬化发生的关键步骤之一。最近的研究表明,一种新的凝集素样氧化低密度脂蛋白受体1(LOX-1)介导ox-LDL的识别和内化。LOX-1是ox-LDL的主要受体,可能在高血压、糖尿病尤其是动脉粥样硬化的发病机制中起重要作用。LOX-1在动脉粥样硬化发病机制中的潜在作用包括:ox-LDL的内吞作用、与动脉粥样硬化相关危险因素共同增强的动脉粥样硬化表达定位、心血管疾病中LOX-1蛋白升高、与动脉粥样硬化相关且被抗动脉粥样硬化药物消除的作用。对LOX-1的鉴定和调控以及对其信号转导途径的了解可能会增进我们对动脉粥样硬化发病机制的认识,并提供一种选择性治疗方法。LOX-1可能是开发新型抗动脉粥样硬化药物的一个潜在且有前景的靶点。然而,由于对LOX-1的了解有限,仍有许多问题有待解答。