Department of Internal Medicine, University of Milan, IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy.
Curr Vasc Pharmacol. 2010 Mar;8(2):285-92. doi: 10.2174/157016110790886965.
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that affects about 1% of the adult population. RA sufferers not only have a high chronic disease burden, but may also experience increased cardiovascular disease (CVD) and mortality as the prevalence of myocardial infarction (MI) is 4 times higher in RA patients than in general population, and there is ample evidence showing that coagulation processes are active in RA. Fibrin accumulation in the synovium is one of the most striking pathological features of rheumatoid synovitis and characteristic RA antibodies such as anti-citrullinated protein antibodies (ACPA) can cross-react with epitopes exposed on fibrin and fibrinogen molecules, and thus impair fibrinolysis. The inflammation, coagulation and fibrinolytic systems are modulated by a common mechanism that includes the involvement of proinflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6). It has long been recognised that extensive cross-talk takes place between the coagulation pathway and the inflammatory process at various levels, and there is growing evidence that this interaction may be relevant to arthritis. Large-scale, long-term studies have shown that anti-TNF-alpha treatment improves the clinical and laboratory measures of disease activity, and reduces local and systemic inflammation. TNF-alpha blockade may therefore also reduce the impaired coagulation and cardiovascular risk associated with RA. This review provides an overview of the pathophysiological role of TNF-alpha in thrombotic mechanisms and the evidence so far available indicating that anti-TNF-alpha treatment can modify cardiovascular risk in RA.
类风湿关节炎（RA）是一种慢性系统性炎症性疾病，影响约 1%的成年人口。RA 患者不仅慢性病负担高，而且可能会增加心血管疾病（CVD）和死亡率，因为 RA 患者心肌梗死（MI）的患病率比一般人群高 4 倍，并且有充分的证据表明凝血过程在 RA 中是活跃的。纤维蛋白在滑膜中的积累是类风湿性滑膜炎最显著的病理特征之一，特征性的 RA 抗体，如抗瓜氨酸化蛋白抗体（ACPA），可以与纤维蛋白和纤维蛋白原分子上暴露的表位发生交叉反应，从而损害纤维蛋白溶解。炎症、凝血和纤维蛋白溶解系统受到共同机制的调节，包括促炎细胞因子（如肿瘤坏死因子-α（TNF-α）和白细胞介素 6（IL-6））的参与。长期以来，人们一直认识到凝血途径和炎症过程在各个层面上存在广泛的相互作用，并且越来越多的证据表明这种相互作用可能与关节炎有关。大规模、长期的研究表明，抗 TNF-α 治疗可改善疾病活动的临床和实验室指标，并降低局部和全身炎症。因此，TNF-α 阻断可能还可以降低 RA 相关的凝血障碍和心血管风险。这篇综述提供了 TNF-α 在血栓形成机制中的病理生理学作用的概述，以及迄今为止表明抗 TNF-α 治疗可以改变 RA 患者心血管风险的证据。
