BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. 2010 Elsevier B.V. All rights reserved.
BACKGROUND: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. METHODS: In an attempt to identify some soluble components differentially expressed in the plasma of HHTpatients, angiopoietin-2 and soluble endoglin concentrations were analyzed with standard quantitative sandwich ELISA. RESULTS:Angiopoietin-2 and soluble endoglin levels are reduced in plasma of HHTpatients compared to control individuals, and a diagnostic algorithm for HHT based on these protein levels is proposed. CONCLUSIONS: 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 HHTpatients. 2010 Elsevier B.V. All rights reserved.
Authors: Ana M Blázquez-Medela; Luis García-Ortiz; Manuel A Gómez-Marcos; José I Recio-Rodríguez; Angel Sánchez-Rodríguez; José M López-Novoa; Carlos Martínez-Salgado Journal: BMC Med Date: 2010-12-20 Impact factor: 8.775
Authors: Luisa Ojeda-Fernández; Lucía Recio-Poveda; Mikel Aristorena; Pedro Lastres; Francisco J Blanco; Francisco Sanz-Rodríguez; Eunate Gallardo-Vara; Mateo de las Casas-Engel; Ángel Corbí; Helen M Arthur; Carmelo Bernabeu; Luisa M Botella Journal: PLoS Genet Date: 2016-03-24 Impact factor: 5.917