Department of Internal Medicine, University of Milan, IRCCS Foundation Maggiore Hospital Policlinico, Mangiagalli, Regina Elena, Italy.
J Autoimmun. 2010 Mar;34(2):105-10. doi: 10.1016/j.jaut.2009.07.004. Epub 2009 Aug 4.
There is strong evidence that antiphospholipid antibodies (aPL) perturb endothelium both in vitro and in experimental animal models. by inducing a vasculopathy and an endothelial pro-inflammatory/coagulant phenotype. However, few contrasting studies raised the issue about the possibility to detect a comparable endothelial perturbation in anti-phospholipid syndrome (APS) patients. The aim of this observational case-control study was to evaluate several parameters of endothelial perturbation in patients with APS and without any other atherosclerosis risk factor.
We investigated plasma levels of soluble adhesion molecules (s-ICAM-1, s-VCAM-1, s-E-selectin), soluble thrombomodulin (sTM), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA) by solid-phase assays in 40 selected APS patients and 40 age- and sex-matched healthy subjects. In addition, we evaluated circulating endothelial cells by flow cytometry and brachial artery flow-mediated vasodilation. Patients and controls were free of conditions known to affect both the biological and the functional endothelial parameters.
Plasma levels of sTM, s-E-selectin and s-VCAM-1 did not differ from controls, while a significant increase in s-ICAM-1 (P = 0.029), t-PA (P = 0.003) and vWF titres (P = 0.002) was found. Circulating mature endothelial cells were also significantly higher in patients than in controls (P = 0.05) and decreased during both vitamin K antagonists (P = 0.001) and antiplatelet (P = 0.032) treatments. Mean brachial artery flow-mediated vasodilation responses were significantly impaired compared to healthy subjects (P = 0.0001).
As a whole these findings indicate that APS patients display an endothelial perturbation in the absence of other detectable traditional risk factors for atherosclerosis.
有强有力的证据表明，抗磷脂抗体（aPL）在体外和实验动物模型中都会扰乱内皮细胞，导致血管病变和内皮促炎/促凝表型。然而，少数对比研究提出了一个问题，即在抗磷脂综合征（APS）患者中是否有可能检测到类似的内皮扰乱。本观察性病例对照研究的目的是评估 APS 患者和无任何其他动脉粥样硬化危险因素的患者的几种内皮紊乱参数。
我们通过固相测定法在 40 名选定的 APS 患者和 40 名年龄和性别匹配的健康受试者中检测了血浆可溶性黏附分子（s-ICAM-1、s-VCAM-1、s-E-选择素）、可溶性血栓调节蛋白（sTM）、血管性血友病因子（vWF）和组织型纤溶酶原激活物（t-PA）的水平。此外，我们通过流式细胞术评估了循环内皮细胞，并检测了肱动脉血流介导的血管舒张功能。患者和对照组均无已知影响生物和功能内皮参数的疾病。
sTM、s-E-选择素和 s-VCAM-1 的血浆水平与对照组无差异，而 s-ICAM-1（P = 0.029）、t-PA（P = 0.003）和 vWF 滴度（P = 0.002）显著增加。与对照组相比，患者的循环成熟内皮细胞也显著升高（P = 0.05），且在接受维生素 K 拮抗剂（P = 0.001）和抗血小板治疗（P = 0.032）时均下降。与健康受试者相比，肱动脉血流介导的血管舒张反应明显受损（P = 0.0001）。
总的来说，这些发现表明 APS 患者在没有其他可检测的动脉粥样硬化传统危险因素的情况下表现出内皮紊乱。
