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Title: Fibrillin 2 is upregulated in the ascending aorta of patients with bicuspid aortic valve.
Authors: Rueda-Martínez, Carmen
Lamas, Oscar
Mataró, María José
Robledo-Carmona, Juan
Sánchez-Espín, Gemma
Moreno-Santos, Inmaculada
Carrasco-Chinchilla, Fernando
Gallego, Pastora
Such-Martínez, Miguel
de Teresa, Eduardo
Jiménez-Navarro, Manuel
Fernández, Borja
Keywords: Aetiology;Aortic aneurysm;Bicuspid aortic valve;Fibrillins;Metalloproteases
metadata.dc.subject.mesh: Aged
Aorta, Thoracic
Aortic Valve
Bicuspid Aortic Valve Disease
Gene Expression Regulation
Heart Valve Diseases
Middle Aged
Real-Time Polymerase Chain Reaction
Issue Date: 15-Sep-2016
Abstract: 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. 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. 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. 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.
metadata.dc.identifier.doi: 10.1093/ejcts/ezw277
Appears in Collections:Producción 2020

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