title: Fibrillin 2 is upregulated in the ascending aorta of patients with bicuspid aortic valve.
abstract: OBJECTIVE
  Bicuspid aortic valve (BAV) is the most prevalent congenital cardiac malformation, frequently associated with aortic dilatation (AD). The molecular mechanisms involved in AD and its aetiological link with BAV formation are poorly understood. Altered fibrillin-1 (FBN1) and metalloprotease-2, -9 (MMP2,9) protein activities have been suggested to be involved in BAV aortopathy. In addition, FBN2 participates in embryonic valve formation, but its possible involvement in BAV-associated AD has never been explored. In this report, we evaluate the expression levels of MMP2,9 and FBN1,2 in the ascending aorta of patients with normal or dilated aortas and with tricuspid aortic valve (TAV) or BAV, using appropriate tissue-specific reference genes.
  
  
  METHODS
  Gene expression was quantified by real-time quantitative polymerase chain reaction in 52 patients, using one or three reference genes previously validated in the same patient population.
  
  
  RESULTS
  FBN2 expression was significantly increased in the aortas of patients with BAV compared with individuals with TAV (0.178 ± 0.042 vs 0.096 ± 0.021, P = 0.015), whereas differences in FBN1 did not reach statistical significance (1.946 ± 0.228 vs 1.430 ± 0.114, P = 0.090). When four groups of samples were considered, FBN2 expression was significantly higher in patients with BAV and AD compared with patients with TAV and AD (0.164 ± 0.035 vs 0.074 ± 0.027, P = 0.040). No significant differences were found when FBN1/FBN2 ratio, and MMP2 and MMP9 expression levels were analysed. No linear relationship between aortic diameter and gene expression levels were found.
  
  
  CONCLUSIONS
  BAV patients have an increased FBN (especially FBN2) gene expression level in the ascending aorta, irrespective of dilatation, whereas MMP expression does not change significantly. These results add a new piece of information to the pathophysiology of BAV disease and point to FBN2 as a new molecular player.
authors.affiliation: UGC del Corazón, Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, RIC (Red de Investigación Cardiovascular), Málaga, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Rueda-Martínez
authors.affiliation: UGC del Corazón, Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, RIC (Red de Investigación Cardiovascular), Málaga, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Lamas
authors.affiliation: UGC del Corazón, Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, RIC (Red de Investigación Cardiovascular), Málaga, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Mataró
authors.affiliation: UGC del Corazón, Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, RIC (Red de Investigación Cardiovascular), Málaga, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Robledo-Carmona
authors.affiliation: UGC del Corazón, Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, RIC (Red de Investigación Cardiovascular), Málaga, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Sánchez-Espín
authors.affiliation: UGC del Corazón, Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, RIC (Red de Investigación Cardiovascular), Málaga, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Moreno-Santos
authors.affiliation: UGC del Corazón, Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, RIC (Red de Investigación Cardiovascular), Málaga, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Carrasco-Chinchilla
authors.affiliation: Unidad de Imagen Cardiaca, Servicio de Cardiología, Hospital Virgen Macarena, UGC Área del Corazón, Sevilla, Spain.
authors.forename: Pastora
authors.initials: P
authors.lastname: Gallego
authors.affiliation: UGC del Corazón, Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, RIC (Red de Investigación Cardiovascular), Málaga, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Such-Martínez
authors.affiliation: UGC del Corazón, Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, RIC (Red de Investigación Cardiovascular), Málaga, Spain.|Departamento de Medicina, Facultad de Medicina, Universidad de Málaga, Málaga, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: de Teresa
authors.affiliation: UGC del Corazón, Instituto de Biomedicina de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, RIC (Red de Investigación Cardiovascular), Málaga, Spain mjimeneznavarro@gmail.com.|Departamento de Medicina, Facultad de Medicina, Universidad de Málaga, Málaga, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Jiménez-Navarro
authors.affiliation: Departamento de Biología Animal, Facultad de Ciencias, Instituto de Biomedicina de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain.
authors.forename: Borja
authors.initials: B
authors.lastname: Fernández
mesh_terms: D000368:Aged; D001013:Aorta, Thoracic / Q000378:metabolism*; D001021:Aortic Valve / Q000002:abnormalities* / Q000378:metabolism; D000082882:Bicuspid Aortic Valve Disease; D005260:Female; D000071840:Fibrillin-2 / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D006349:Heart Valve Diseases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D000071840:Fibrillin-2; D012313:RNA
keywords: Aetiology; Aortic aneurysm; Bicuspid aortic valve; Fibrillins; Metalloproteases