title: Gene expression fingerprinting for human hereditary hemorrhagic telangiectasia.
abstract: Hereditary hemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu syndrome is an autosomal dominant vascular disorder characterized by telangiectases and internal arteriovenous malformations. It is caused by mutations in elements of the transforming growth factor-beta (TGF-beta) receptor complex: endoglin, a co-receptor, responsible for HHT1, or ALK1 (activin receptor-like kinase 1), a type I receptor leading to HHT2. Recently, we have established cultures of HHT endothelial cells, primary targets of the disease. These cells showed deficient TGF-beta signaling and angiogenesis, representing a useful human model to study the molecular mechanism of this disease. To understand the pathogenic mechanism underlying HHT, we have used total RNA probes to compare HHT versus non-HHT cells by expression microarrays. This work represents a systematic study to identify target genes affected in HHT cells. Given the similarity of symptoms in HHT1 and HHT2, special interest has been put on the identification of common targets for both HHT types. As a result, 277 downregulated and 63 upregulated genes were identified in HHT versus control cells. These genes are involved in biological processes relevant to the HHT pathology, such as angiogenesis, cytoskeleton, cell migration, proliferation and NO synthesis. The type of misregulated genes found in HHT endothelial cells lead us to propose a model of HHT pathogenesis, opening new perspectives to understand this disorder. Moreover, as the disease is originated by mutations in proteins of the TGF-beta receptor complex, these results may be useful to find out targets of the TGF-beta pathway in endothelium.
authors.affiliation: Centro de Investigaciones Biológicas, CSIC, Madrid, Spain, 2 Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
authors.forename: Africa
authors.initials: A
authors.lastname: Fernandez-L
authors.forename: Africa
authors.initials: A
authors.lastname: Fernandez-Lopez
authors.forename: Eva M
authors.initials: EM
authors.lastname: Garrido-Martin
authors.forename: Francisco
authors.initials: F
authors.lastname: Sanz-Rodriguez
authors.forename: Miguel
authors.initials: M
authors.lastname: Pericacho
authors.forename: Alicia
authors.initials: A
authors.lastname: Rodriguez-Barbero
authors.forename: Nelida
authors.initials: N
authors.lastname: Eleno
authors.forename: Jose M
authors.initials: JM
authors.lastname: Lopez-Novoa
authors.forename: Anette
authors.initials: A
authors.lastname: Düwell
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Vega
authors.forename: Carmelo
authors.initials: C
authors.lastname: Bernabeu
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Botella
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000378:metabolism; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic; D015398:Signal Transduction; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014945:Wound Healing
chemical_list: D016212:Transforming Growth Factor beta