Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples Federico II, Naples, Italy.
Department of Biomedical and Clinical Sciences Luigi Sacco, Luigi Sacco Hospital Milan, University of Milan, Milan, Italy.
Allergy. 2016 Jul;71(7):989-96. doi: 10.1111/all.12862. Epub 2016 Mar 17.
Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is a rare inherited genetic disease characterized by recurrent swelling episodes of the skin, gastrointestinal tract, and upper airways. Angioedema attacks result from increased vascular permeability due to the release of bradykinin from high molecular weight kininogen. Currently, there are no biomarkers predicting the frequency of angioedema attacks. Vascular permeability is modulated by several factors, including vascular endothelial growth factors (VEGFs) and angiopoietins (Angs). As increased circulating levels of VEGFs and Angs have been observed in diseases associated with higher vascular permeability (e.g., systemic capillary leak syndrome and sepsis), we sought to analyze plasma concentrations of VEGFs and Angs in patients with C1-INH-HAE.
Sixty-eight healthy controls and 128 patients with C1-INH-HAE were studied. Concentrations of angiogenic (VEGF-A, Ang1, Ang2), anti-angiogenic (VEGF-A165b ) and lymphangiogenic (VEGF-C) factors were evaluated by ELISA. C1-INH functional activity was assessed by EIA.
Plasma concentrations of VEGF-A, VEGF-C, Ang1, and Ang2 were higher in patients with C1-INH-HAE in remission than in healthy controls. Concentration of VEGF-A was further increased in patients with lower C1-INH functional activity. Patients with C1-INH-HAE experiencing more than 12 angioedema attacks per year were characterized by higher plasma levels of VEGF-A, VEGF-C, and Ang2 compared with the other patients.
We hypothesize that VEGFs and Angs induce a state of 'vascular preconditioning' that may predispose to angioedema attacks. In addition, the identification of increased plasma levels of VEGFs and Angs in patients with C1-INH-HAE may prompt the investigation of VEGFs and Angs as biomarkers of C1-INH-HAE severity.
C1 抑制剂缺乏遗传性血管水肿（C1-INH-HAE）是一种罕见的遗传性遗传疾病，其特征是皮肤、胃肠道和上呼吸道反复出现肿胀发作。血管水肿发作是由于高分子量激肽原释放缓激肽导致血管通透性增加所致。目前，尚无预测血管水肿发作频率的生物标志物。血管通透性受多种因素调节，包括血管内皮生长因子（VEGFs）和血管生成素（Angs）。由于在与更高血管通透性相关的疾病（例如全身性毛细血管渗漏综合征和败血症）中观察到循环中 VEGFs 和 Angs 水平升高，我们试图分析 C1-INH-HAE 患者的血浆 VEGFs 和 Angs 浓度。
研究了 68 名健康对照者和 128 名 C1-INH-HAE 患者。通过 ELISA 评估血管生成（VEGF-A、Ang1、Ang2）、抗血管生成（VEGF-A165b）和淋巴管生成（VEGF-C）因子的浓度。通过 EIA 评估 C1-INH 功能活性。
缓解期 C1-INH-HAE 患者的血浆 VEGF-A、VEGF-C、Ang1 和 Ang2 浓度高于健康对照组。C1-INH 功能活性较低的患者 VEGF-A 浓度进一步升高。每年发生超过 12 次血管水肿发作的 C1-INH-HAE 患者的 VEGF-A、VEGF-C 和 Ang2 血浆水平高于其他患者。
我们假设 VEGFs 和 Angs 诱导“血管预适应”状态，可能导致血管水肿发作。此外，在 C1-INH-HAE 患者中发现 VEGFs 和 Angs 血浆水平升高可能促使研究将 VEGFs 和 Angs 作为 C1-INH-HAE 严重程度的生物标志物。
