风湿免疫性疾病中的血管内皮功能障碍。

Endothelial dysfunction in rheumatic autoimmune diseases.

机构信息

Department of Internal Medicine, Viale Benedetto XV, n. 6, University of Genoa, 16132 Genoa, Italy.

出版信息

Atherosclerosis. 2012 Oct;224(2):309-17. doi: 10.1016/j.atherosclerosis.2012.05.013. Epub 2012 May 18.

Abstract

Rheumatic autoimmune diseases have been associated with accelerated atherosclerosis and various types of vasculopathies. Atherosclerosis is an inflammatory condition which starts as a "response to injury" favoring endothelial dysfunction which is associated with increased expression of adhesion molecules, pro-inflammatory cytokines, pro-thrombotic factors, oxidative stress upregulation and abnormal vascular tone modulation. Endothelial dysfunction in rheumatic autoimmune diseases involves innate immune responses, including macrophages and dendritic cells expression of scavenger and toll-like receptors for modified or native LDL as well as neutrophil and complement activation, and dysregulation of adaptive immune responses, including proliferation of autoreactive T-helper-1 lymphocytes and defective function of dendritic and regulatory T cells. Specific differences for endothelial function among different disorders include: a) increased amounts of pro-atherogenic hormones, decreased amounts of anti-atherogenic hormones and increased insulin resistance in rheumatoid arthritis; b) autoantibodies production in systemic lupus erythematosus and antiphospholipid syndrome; c) smooth muscle cells proliferation, destruction of internal elastic lamina, fibrosis and coagulation and fibrinolytic system dysfunction in systemic sclerosis. Several self-antigens (i.e. high density lipoproteins, heat shock proteins, β2-glycoprotein1) and self-molecules modified by oxidative events (i.e. low density lipoproteins and oxidized hemoglobin) have been identified as targets of autoimmune responses. Endothelial dysfunction leads to accelerated atherosclerosis in rheumatoid arthritis, systemic lupus erythematosus and spondyloarthropaties whereas obliterative vasculopathy is associated with systemic sclerosis. In this paper, we will briefly review the most relevant information upon endothelial dysfunction and inflammatory mechanisms in atherosclerosis and we will summarize the similarities and differences in vascular disease patterns underlying different rheumatic autoimmune diseases.

摘要

风湿免疫性疾病与动脉粥样硬化和各种血管病变的加速发展有关。动脉粥样硬化是一种炎症状态,始于“对损伤的反应”,有利于内皮功能障碍,这与粘附分子、促炎细胞因子、促血栓形成因子、氧化应激上调和血管张力调节异常的表达增加有关。风湿免疫性疾病中的内皮功能障碍涉及固有免疫反应,包括巨噬细胞和树突状细胞对修饰或天然 LDL 的清道夫和 Toll 样受体的表达,以及中性粒细胞和补体的激活,以及适应性免疫反应的失调,包括自身反应性辅助性 T 淋巴细胞的增殖和树突状和调节性 T 细胞的功能缺陷。不同疾病中内皮功能的具体差异包括:a)类风湿关节炎中促动脉粥样硬化激素含量增加,抗动脉粥样硬化激素含量减少,胰岛素抵抗增加;b)系统性红斑狼疮和抗磷脂综合征中的自身抗体产生;c)系统性硬化症中的平滑肌细胞增殖、内弹性膜破坏、纤维化和凝血及纤维蛋白溶解系统功能障碍。已经确定了几种自身抗原(即高密度脂蛋白、热休克蛋白、β2-糖蛋白 1)和氧化事件修饰的自身分子(即低密度脂蛋白和氧化血红蛋白)作为自身免疫反应的靶标。内皮功能障碍导致类风湿关节炎、系统性红斑狼疮和脊柱关节病中的动脉粥样硬化加速,而闭塞性血管病变与系统性硬化症有关。在本文中,我们将简要回顾动脉粥样硬化中内皮功能障碍和炎症机制的最相关信息,并总结不同风湿免疫性疾病中血管疾病模式的相似性和差异。

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