Morawietz H
Bereich Gefässendothel/Mikrozirkulation, Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus Dresden.
Dtsch Med Wochenschr. 2010 Feb;135(7):308-12. doi: 10.1055/s-0029-1244854. Epub 2010 Feb 9.
Atherosclerosis with its complications like heart attack and stroke, is the most frequent cause of death in the industrialized countries. Oxidized low-density lipoproteins (LDL) play a major role in the pathogenesis of atherosclerosis. Inhibition of cholesterol synthesis by statins has several protective effects but is not sufficient to prevent the uptake of oxidized LDL and the development of atherosclerotic plaques. For this reason a selective pharmacological inhibition of the uptake of oxidized LDL (oxLDL) in endothelial cells is an interesting therapeutic approach. An important novel target molecule is the endothelial lectin-like oxLDL receptor LOX-1. This receptor is able to take up both minimally and highly oxidized LDL. In addition it mediates endothelial phagocytosis of aged and apoptotic cells and plays a role in thrombocyte adhesion and in the interaction between bacterial proteins and endothelial cells in sepsis. LOX-1 is induced by proinflammatory cytokines, oxLDL, angiotensin II, endothelin-1 and arterial hypertension. LOX-1 increases endothelial dysfunction and atherosclerosis by endothelial uptake of oxLDL. This is the reason why LOX-1 has been considered as a novel link between hypertension and atherosclerosis. Transgenic overexpression of the LOX-1 receptor and high-fat diet induces intramyocardial vascular disease and endothelial dysfunction in resistance arteries. In contrast, genetic deletion of the LOX-1 gene reduces the development of atherosclerotic plaques. In the clinical context LOX-1 has been detected in the early phase of endothelial dysfunction and atherosclerosis in arteries of patients with coronary heart disease. Several novel data support a role of LOX-1 in the endothelial dysfunction in diabetic vascular and renal disease, hypercholesterolemia, obesity and preeclampsia. This makes the LOX-1 receptor a novel and interesting target molecule in endothelial dysfunction and atherosclerosis.
动脉粥样硬化及其诸如心脏病发作和中风等并发症，是工业化国家最常见的死亡原因。氧化型低密度脂蛋白（LDL）在动脉粥样硬化的发病机制中起主要作用。他汀类药物抑制胆固醇合成有多种保护作用，但不足以阻止氧化型LDL的摄取和动脉粥样硬化斑块的形成。因此，选择性药理抑制内皮细胞中氧化型LDL（oxLDL）的摄取是一种有趣的治疗方法。一个重要的新型靶分子是内皮凝集素样氧化型LDL受体LOX-1。该受体能够摄取轻度和高度氧化的LDL。此外，它介导衰老和凋亡细胞的内皮吞噬作用，并在血小板黏附以及脓毒症中细菌蛋白与内皮细胞之间的相互作用中发挥作用。LOX-1由促炎细胞因子、氧化型LDL、血管紧张素II、内皮素-1和动脉高血压诱导产生。LOX-1通过内皮摄取氧化型LDL增加内皮功能障碍和动脉粥样硬化。这就是为什么LOX-1被认为是高血压和动脉粥样硬化之间的新型联系。LOX-1受体的转基因过表达和高脂饮食会诱导心肌内血管疾病和阻力动脉的内皮功能障碍。相反，LOX-1基因的基因缺失会减少动脉粥样硬化斑块的形成。在临床情况下，已在冠心病患者动脉内皮功能障碍和动脉粥样硬化的早期阶段检测到LOX-1。一些新数据支持LOX-1在糖尿病血管和肾脏疾病、高胆固醇血症、肥胖症和先兆子痫的内皮功能障碍中起作用。这使得LOX-1受体成为内皮功能障碍和动脉粥样硬化中一个新型且有趣的靶分子。
