Hofmann Anja, Brunssen Coy, Morawietz Henning
Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital and Medical Faculty Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital and Medical Faculty Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
Vascul Pharmacol. 2017 Oct 19. doi: 10.1016/j.vph.2017.10.002.
The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major receptor for binding and uptake of oxidized low-density lipoprotein (oxLDL) in endothelial cells. LOX-1 is also expressed in macrophages, smooth muscle cells and platelets. Following internalization of oxLDL, LOX-1 initiates a vicious cycle from activation of pro-inflammatory signaling pathways, thus promoting an increased reactive oxygen species formation and secretion of pro-inflammatory cytokines. LOX-1 plays a pivotal role in the development of endothelial dysfunction, foam cell and advanced lesions formation as well as in myocardial ischemia. Furthermore, it is known that LOX-1 plays a pivotal role in mitochondrial DNA damage, vascular cell apoptosis, and autophagy. A large number of studies provide evidence of a LOX-1's role in endothelial dysfunction, hypertension, diabetes, and obesity. In addition, novel insights into LOX-1 ligands and the activated signaling pathways have been gained. Recent studies have shown an interaction of LOX-1 with microRNA's, thus providing novel tools to regulate LOX-1 function. Because LOX-1 is increased in atherosclerotic plaques and contributes to endothelial dysfunction, several compounds were tested in vivo and in vitro to modulate the LOX-1 expression in therapeutic approaches.
凝集素样氧化低密度脂蛋白受体1（LOX-1）是内皮细胞中结合和摄取氧化低密度脂蛋白（oxLDL）的主要受体。LOX-1也在巨噬细胞、平滑肌细胞和血小板中表达。oxLDL内化后，LOX-1从促炎信号通路的激活开始引发恶性循环，从而促进活性氧生成增加和促炎细胞因子分泌。LOX-1在内皮功能障碍、泡沫细胞和晚期病变形成以及心肌缺血的发展中起关键作用。此外，已知LOX-1在线粒体DNA损伤、血管细胞凋亡和自噬中起关键作用。大量研究提供了LOX-1在内皮功能障碍、高血压、糖尿病和肥胖中作用的证据。此外，对LOX-1配体和激活的信号通路有了新的认识。最近的研究表明LOX-1与微小RNA相互作用，从而提供了调节LOX-1功能的新工具。由于LOX-1在动脉粥样硬化斑块中增加并导致内皮功能障碍，因此在体内和体外测试了几种化合物，以在治疗方法中调节LOX-1表达。
