Reduced plasma levels of Ang-2 and sEng as novel biomarkers in hereditary hemorrhagic telangiectasia (HHT).
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.
Ojeda-Fernandez
Luisa
L
Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain.
Barrios
Laura
L
Rodriguez-Barbero
Alicia
A
Recio-Poveda
Lucia
L
Bernabeu
Carmelo
C
Botella
Luisa M
LM
D000328:Adult; D000368:Aged; D042702:Angiopoietin-2 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D016002:Discriminant Analysis; D000071063:Endoglin; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011956:Receptors, Cell Surface / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012995:Solubility; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055815:Young Adult
D042702:Angiopoietin-2; D015703:Antigens, CD; D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta