Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain.
Clin Chim Acta. 2010 Apr 2;411(7-8):494-9. doi: 10.1016/j.cca.2009.12.023. Epub 2010 Jan 11.
Hereditary hemorrhagic telangiectasia (HHT; OMIM 187300) is an autosomal dominant vascular disorder characterized by telangiectases and internal arteriovenous malformations caused by mutations in certain elements of the TGF-beta receptor complex. In the case of HHT1 mutations in the endoglin gene are responsible, whereas mutations in the ALK1 gene (an activin receptor-like kinase 1), lead to HHT2. Another two loci found at chromosome 5 and chromosome 7, whose target genes remain unidentified, lead to types 3 and 4 of the disease, respectively. Mutations in the MADH4/SMAD4 gene, another member of the TGF-beta signalling pathway, lead to a combined syndrome of familial juvenile polyposis associated with HHT.
In an attempt to identify some soluble components differentially expressed in the plasma of HHT patients, angiopoietin-2 and soluble endoglin concentrations were analyzed with standard quantitative sandwich ELISA.
Angiopoietin-2 and soluble endoglin levels are reduced in plasma of HHT patients compared to control individuals, and a diagnostic algorithm for HHT based on these protein levels is proposed.
Down-regulated protein levels of angiopoietin-2 and soluble endoglin in plasma represent novel HHT biomarkers that could be useful in the biochemical diagnosis of HHT facilitating the rapid identification of potential HHT patients.
遗传性出血性毛细血管扩张症（HHT；OMIM 187300）是一种常染色体显性血管疾病，其特征为毛细血管扩张和由 TGF-β 受体复合物的某些成分突变引起的动静脉畸形。在 HHT1 中，内皮糖蛋白基因突变负责，而 ALK1 基因突变（激活素受体样激酶 1）导致 HHT2。另外两个位于染色体 5 和染色体 7 的位点，其靶基因尚未确定，分别导致疾病的 3 型和 4 型。MADH4/SMAD4 基因突变，TGF-β 信号通路的另一个成员，导致家族性青少年息肉病相关的 HHT 联合综合征。
为了鉴定 HHT 患者血浆中差异表达的某些可溶性成分，采用标准定量夹心 ELISA 法分析血管生成素-2 和可溶性内皮糖蛋白浓度。
与对照组相比，HHT 患者的血浆中血管生成素-2 和可溶性内皮糖蛋白水平降低，并提出了基于这些蛋白水平的 HHT 诊断算法。
血浆中血管生成素-2 和可溶性内皮糖蛋白水平的下调代表了新的 HHT 生物标志物，可用于 HHT 的生化诊断，有助于快速识别潜在的 HHT 患者。
