3rd Department of Medicine, Medical and Health Science Center, University of Debrecen, Moricz Zs, Str, 22, Debrecen 4032, Hungary.
Arthritis Res Ther. 2010;12(3):R78. doi: 10.1186/ar2999. Epub 2010 May 6.
The aim of the present study was to investigate the association between cardiovascular risk factors and endothelial dysfunction in patients with mixed connective tissue disease (MCTD) and to determine which biomarkers are associated with atherosclerotic complications, such as cardiovascular disease.
Fifty MCTD patients and 38 healthy age-matched and sex-matched controls were enrolled in this study. In order to describe endothelial dysfunction, we assessed flow-mediated dilation (FMD), nitrate-mediated dilation (NMD) and carotid artery intima-media thickness (IMT). We investigated FMD of the brachial artery after reactive hyperemia and NMD after sublingual nitroglycerin administration, while the IMT of the common carotid artery was determined by ultrasound. Anti-U1 ribonucleoprotein (anti-U1RNP) antibodies, anti-cardiolipin (anti-CL) antibodies, anti-endothelial cell antibody (AECA) and endothelial cell markers, such as soluble thrombomodulin (TM) and von Willebrand factor antigen (vWFAg), were assessed.
The endothelium-dependent vasodilation (FMD) was significantly impaired in patients with MCTD, as compared with controls (%FMD: 4.7+/-4.2% vs. 8.7+/-5.0%; P<0.001), while the percentage NMD did not differ (%NMD: 14.3+/-6.6% vs. 17.1+/-6.7%; P=0.073). Mean carotid IMT values were higher in patients than in controls (IMT: MCTD, 0.64+/-0.13 mm vs. controls, 0.53+/-0.14 mm; P<0.001). FMD negatively correlated with disease duration, the levels of apolipoprotein A1, the paraoxonase-1 activity, and systolic blood pressure in MCTD patients. The percentage FMD was significantly lower in MCTD patients with cardiovascular diseases (CVD), than in those without CVD (%FMD: 3.5+/-2.9 vs. 5.8+/-4.8, P<0.0002), while percentage NMD did not differ between patients with and without CVDs. Serum levels of autoantibodies (anti-U1RNP, AECA and anti-CL) were significantly higher in MCTD patients and differed between MCTD patients with and without CVD. Endothelial cell markers such as soluble TM (12.2+/-8.1 ng/ml vs. 3.2+/-1.3 ng/ml; P<0.001) and vWFAg (224.1+/-115% vs. 89.4+/-27.1%, P<0.001) were the highest in MCTD patients with CVD.
FMD is a reliable sensitive marker of endothelial cell dysfunction in MCTD. Beside the traditional risk factors, anti-U1RNP, AECA and anti-CL antibodies may be important not only in the pathogenesis of MCTD but in the induction of endothelial cell activation, and may play crucial roles in the development of early atherosclerosis in MCTD.
本研究旨在探讨心血管危险因素与混合性结缔组织病（MCTD）患者内皮功能障碍之间的关系，并确定哪些生物标志物与心血管疾病等动脉粥样硬化并发症相关。
本研究纳入了 50 例 MCTD 患者和 38 名年龄和性别匹配的健康对照者。为了描述内皮功能障碍，我们评估了血流介导的扩张（FMD）、硝酸盐介导的扩张（NMD）和颈动脉内膜中层厚度（IMT）。我们在肱动脉反应性充血后评估了 FMD，在舌下给予硝酸甘油后评估了 NMD，同时通过超声测量颈总动脉 IMT。评估了抗 U1 核糖核蛋白（抗-U1RNP）抗体、抗心磷脂（抗-CL）抗体、抗内皮细胞抗体（AECA）和内皮细胞标志物，如可溶性血栓调节蛋白（TM）和血管性血友病因子抗原（vWFAg）。
与对照组相比，MCTD 患者的内皮依赖性血管舒张（FMD）明显受损（%FMD：4.7+/-4.2% vs. 8.7+/-5.0%；P<0.001），而 NMD 的百分比没有差异（%NMD：14.3+/-6.6% vs. 17.1+/-6.7%；P=0.073）。与对照组相比，MCTD 患者的平均颈动脉 IMT 值更高（IMT：MCTD，0.64+/-0.13 mm vs. 对照组，0.53+/-0.14 mm；P<0.001）。FMD 与 MCTD 患者的疾病持续时间、载脂蛋白 A1 水平、对氧磷酶-1 活性和收缩压呈负相关。与无 CVD 的 MCTD 患者相比，有 CVD 的 MCTD 患者的 FMD 百分比明显更低（%FMD：3.5+/-2.9 vs. 5.8+/-4.8，P<0.0002），而 NMD 的百分比在有和无 CVD 的患者之间没有差异。MCTD 患者的自身抗体（抗-U1RNP、AECA 和抗-CL）水平明显高于对照组，且有和无 CVD 的 MCTD 患者之间存在差异。内皮细胞标志物，如可溶性 TM（12.2+/-8.1 ng/ml vs. 3.2+/-1.3 ng/ml；P<0.001）和 vWFAg（224.1+/-115% vs. 89.4+/-27.1%，P<0.001）在有 CVD 的 MCTD 患者中最高。
FMD 是 MCTD 内皮细胞功能障碍的一种可靠的敏感标志物。除了传统的危险因素外，抗 U1RNP、AECA 和抗-CL 抗体不仅在 MCTD 的发病机制中很重要，而且在诱导内皮细胞激活方面也很重要，可能在 MCTD 早期动脉粥样硬化的发展中起关键作用。
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