未分化结缔组织病患者的内皮功能受损：一项随访研究。
Impaired endothelial function in patients with undifferentiated connective tissue disease: a follow-up study.
作者信息
Laczik Renata, Soltesz Pal, Szodoray Peter, Szekanecz Zoltan, Kerekes Gyorgy, Paragh Gyorgy, Rajnavölgyi Eva, Abel Gyorgy, Szegedi Gyula, Bodolay Edit
机构信息
Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen Clinical Centre, Department of Immunology, University of Debrecen Clinical Centre, Hungary, Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway, Division of Rheumatology, Department of Internal Medicine, University of Debrecen Clinical Centre, Division of Metabolic Diseases, Department of Medicine, University of Debrecen Clinical Centre, Hungary and Department of Laboratory Medicine, Lahey Clinic, Boston, MA, USA Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen Clinical Centre, Department of Immunology, University of Debrecen Clinical Centre, Hungary, Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway, Division of Rheumatology, Department of Internal Medicine, University of Debrecen Clinical Centre, Division of Metabolic Diseases, Department of Medicine, University of Debrecen Clinical Centre, Hungary and Department of Laboratory Medicine, Lahey Clinic, Boston, MA, USA.
Division of Clinical Immunology, Department of Internal Medicine, University of Debrecen Clinical Centre, Department of Immunology, University of Debrecen Clinical Centre, Hungary, Institute of Immunology, Rikshospitalet, University of Oslo, Oslo, Norway, Division of Rheumatology, Department of Internal Medicine, University of Debrecen Clinical Centre, Division of Metabolic Diseases, Department of Medicine, University of Debrecen Clinical Centre, Hungary and Department of Laboratory Medicine, Lahey Clinic, Boston, MA, USA.
出版信息
Rheumatology (Oxford). 2014 Nov;53(11):2035-43. doi: 10.1093/rheumatology/keu236. Epub 2014 Jun 10.
OBJECTIVE
In this study the alteration of endothelial function, arterial stiffness and autoantibodies was investigated in patients with UCTD.
METHODS
Thirty-one patients with UCTD were included in this prospective study. All the patients remained in the UCTD stage during the average 3.8 years follow-up period. The onset of UCTD was denoted as UCTD1, while the end of the follow-up period was called UCTD2. Flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT), autoantibodies [such as anti-SSA, anti-SSB, anti-DNA, anti-RNP, anti-CCP, aCL, anti-oxidized low-density lipoprotein (oxLDL) and AECA], von Willebrand factor antigen, thrombomodulin (TM), endothelin 1 (ET-1) and lipid parameters were measured.
RESULTS
In the UCTD1 stage, high-sensitivity CRP (hsCRP) and endothelial cell activation and/or damage markers such as TM, ET-1 and AECA levels were significantly higher compared with controls (controls vs UCTD1: hsCRP, P < 0.0001; TM, P = 0.001; ET-1, P < 0.0001). In the UCTD2 stage, the carotid IMT increased (UCTD1 vs UCTD2, P = 0.01) and FMD further deteriorated (UCTD1 and UCTD2, P = 0.001). In UCTD2 there was a close correlation between the carotid IMT, and duration of the disease (r = 0.612, P < 0.001), the level of TM (r = 0.673, P < 0.001) and anti-oxLDL (r = 0.800, P < 0.001).
CONCLUSION
Our data suggest that the presence of inflammation and autoantibodies provoke endothelial cell activation and/or injury in UCTD patients. The persistent endothelial dysfunction may provoke the development of atherosclerosis. FMD was found to be the most sensitive marker for arterial stiffness, and the increase of IMT clearly indicated the existence of preclinical atherosclerosis in UCTD patients.
目的
本研究旨在调查未分化结缔组织病（UCTD）患者的内皮功能、动脉僵硬度和自身抗体的变化。
方法
31例UCTD患者纳入本前瞻性研究。在平均3.8年的随访期内，所有患者均处于UCTD阶段。UCTD发病时记为UCTD1，随访期末记为UCTD2。测量血流介导的血管舒张（FMD）、颈动脉内膜中层厚度（IMT）、自身抗体[如抗SSA、抗SSB、抗DNA、抗RNP、抗CCP、抗心磷脂（aCL）、抗氧化型低密度脂蛋白（oxLDL）和抗内皮细胞抗体（AECA）]、血管性血友病因子抗原、血栓调节蛋白（TM）、内皮素1（ET-1）和血脂参数。
结果
在UCTD1阶段，与对照组相比，高敏C反应蛋白（hsCRP）以及内皮细胞活化和/或损伤标志物如TM、ET-1和AECA水平显著升高（对照组与UCTD1：hsCRP，P<0.0001；TM，P = 0.001；ET-1，P<0.0001）。在UCTD2阶段，颈动脉IMT增加（UCTD1与UCTD2，P = 0.01），FMD进一步恶化（UCTD1和UCTD2，P = 0.001）。在UCTD2阶段，颈动脉IMT与病程（r = 0.612，P<0.001）、TM水平（r = 0.673，P<0.001）和抗oxLDL（r = 0.800，P<0.001）之间存在密切相关性。
结论
我们的数据表明，炎症和自身抗体的存在会引发UCTD患者的内皮细胞活化和/或损伤。持续的内皮功能障碍可能会引发动脉粥样硬化的发展。发现FMD是动脉僵硬度最敏感的标志物，IMT增加清楚地表明UCTD患者存在临床前期动脉粥样硬化。
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