Hahn B H, McMahon M
David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
Lupus. 2008 May;17(5):368-70. doi: 10.1177/0961203308089989.
The accelerated atherosclerosis that occurs in some patients with systemic lupus erythematosus (SLE) has a complex pathogenesis, including alterations in lipids, inflammation and the immune system. In this article, we review the evidence that peroxidase-related alteration of normal, protective high-density lipoprotein (HDL) converts them to pro-inflammatory HDL (piHDL), characterized by lower content of the cholesterol transport lipoprotein ApoA1 and impaired function of the antioxidant enzyme paroxonase, which prevents oxidation of low-density lipoprotein (LDL). Forty-five per cent of women with SLE have piHDL compared with 20% of patients with rheumatoid arthritis and 4% of healthy controls. The presence of piHDL increases risk for coronary artery events and carotid artery plaque. Another result of lipid oxidation in patients with SLE is generation of highly oxidized LDL and phospholipids (PL), probably stimulating antibodies to OxPL phospholipids. These antibodies along with promoting thrombosis also interfere with deposits of Annexin V onto endothelial cells, which probably promote increased instability of atherosclerotic plaque. Thus, piHDL and anti-OxPL promote plaque formation, plaque instability and thrombosis, accounting for some of the large increase in atherosclerosis and coronary artery events in SLE.
一些系统性红斑狼疮（SLE）患者出现的动脉粥样硬化加速具有复杂的发病机制，包括脂质、炎症和免疫系统的改变。在本文中，我们回顾了相关证据，即正常的、具有保护作用的高密度脂蛋白（HDL）的过氧化物酶相关改变将其转化为促炎性HDL（piHDL），其特征是胆固醇转运脂蛋白ApoA1含量较低，抗氧化酶对氧磷酶功能受损，而对氧磷酶可防止低密度脂蛋白（LDL）氧化。45%的SLE女性患者存在piHDL，相比之下，类风湿性关节炎患者的这一比例为20%，健康对照者为4%。piHDL的存在增加了冠状动脉事件和颈动脉斑块的风险。SLE患者脂质氧化的另一个结果是产生高度氧化的LDL和磷脂（PL），可能会刺激针对氧化磷脂（OxPL）的抗体产生。这些抗体除了促进血栓形成外，还会干扰膜联蛋白V在内皮细胞上的沉积，这可能会促进动脉粥样硬化斑块不稳定性增加。因此，piHDL和抗OxPL促进斑块形成、斑块不稳定性和血栓形成，这也是SLE患者动脉粥样硬化和冠状动脉事件大幅增加的部分原因。
