Mak Anselm, Kow Nien Yee
Division of Rheumatology, Department of Medicine, University Medicine Cluster, 1E Kent Ridge Road, Level 10, NUHS Tower Block, Singapore 119228 ; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.
Biomed Res Int. 2014;2014:178721. doi: 10.1155/2014/178721. Epub 2014 Mar 26.
Atherosclerosis is accelerated in patients with systemic lupus erythematosus (SLE) and it leads to excessive cardiovascular complications in these patients. Despite the improved awareness of cardiovascular disease and advent of clinical diagnostics, the process of atherogenesis in most patients remains clinically silent until symptoms and signs of cardiovascular complications develop. As evidence has demonstrated that vascular damage is already occurring before clinically overt cardiovascular disease develops in lupus patients, intervention at the preclinical stage of atherogenesis would be plausible. Indeed, endothelial dysfunction, one of the earliest steps of atherogenesis, has been demonstrated to occur in lupus patients even when they are naïve for cardiovascular disease. Currently known "endothelium-toxic" factors including type 1 interferon, proinflammatory cytokines, inflammatory cells, immune complexes, costimulatory molecules, neutrophils extracellular traps, lupus-related autoantibodies, oxidative stress, and dyslipidemia, coupled with the aberrant functions of the endothelial progenitor cells (EPC) which are crucial to vascular repair, likely tip the balance towards endothelial dysfunction and propensity to develop cardiovascular disease in lupus patients. In this review, altered physiology of the endothelium, factors leading to perturbed vascular repair contributed by lupus EPC and the impact of proatherogenic factors on the endothelium which potentially lead to atherosclerosis in lupus patients will be discussed.
系统性红斑狼疮（SLE）患者的动脉粥样硬化进程会加速，这会导致这些患者出现过多的心血管并发症。尽管人们对心血管疾病的认识有所提高，临床诊断方法也不断涌现，但在大多数患者中，动脉粥样硬化的进程在临床上仍处于隐匿状态，直到出现心血管并发症的症状和体征。有证据表明，在狼疮患者出现临床明显的心血管疾病之前，血管损伤就已经发生，因此在动脉粥样硬化的临床前期进行干预是可行的。事实上，即使狼疮患者尚未患有心血管疾病，动脉粥样硬化最早的步骤之一——内皮功能障碍，也已在他们身上得到证实。目前已知的“内皮毒性”因素包括1型干扰素、促炎细胞因子、炎症细胞、免疫复合物、共刺激分子、中性粒细胞胞外陷阱、狼疮相关自身抗体、氧化应激和血脂异常，再加上对血管修复至关重要的内皮祖细胞（EPC）功能异常，可能会使狼疮患者更容易出现内皮功能障碍和发生心血管疾病。在这篇综述中，我们将讨论内皮生理的改变、狼疮EPC导致血管修复紊乱的因素以及促动脉粥样硬化因素对内皮的影响，这些因素可能会导致狼疮患者发生动脉粥样硬化。
