Reduced aggrecan expression affects cardiac outflow tract development in zebrafish and is associated with bicuspid aortic valve disease in humans

Pierre Rambeau; Emilie Faure; Alexis Theron; Jean-François Avierinos; Chris Jopling; Stéphane Zaffran; Adèle Faucherre

doi:10.1016/j.ijcard.2017.09.174

Reduced aggrecan expression affects cardiac outflow tract development in zebrafish and is associated with bicuspid aortic valve disease in humans

Pierre Rambeau ¹ Emilie Faure ² Alexis Theron ^{2, 3} Jean-François Avierinos ^{4, 2} Chris Jopling ¹ Stéphane Zaffran ² Adèle Faucherre ^{1, *}

* Auteur correspondant

1 IGF - Institut de Génomique Fonctionnelle

2 GMGF - Génétique Médicale et Génomique Fonctionnelle

3 Service de chirurgie cardiaque

4 Service de cardiologie

Abstract : Available online xxxx Hemodynamic forces have been known for a long time to regulate cardiogenic processes such as cardiac valve development. During embryonic development in vertebrates, the outflow tract (OFT) adjacent to the ventricle comes under increasing hemodynamic load as cardiogenesis proceeds. Consequently, extracellular matrix components are produced in this region as the cardiac cushions form which will eventually give rise to the aortic valves. The proteoglycan AGGRECAN is a key component of the aortic valves and is frequently found to be deregulated in a variety of aortic valve diseases. Here we demonstrate that aggrecan expression in the OFT of developing zebrafish embryos is hemodynamically dependent, a process presumably mediated by mechanosensitive channels. Furthermore, knockdown or knockout of aggrecan leads to failure of the OFT to develop resulting in ste-nosis. Based on these findings we analysed the expression of AGGRECAN in human bicuspid aortic valves (BAV). We found that in type 0 BAV there was a significant reduction in the expression of AGGRECAN. Our data indicate that aggrecan is required for OFT development and when its expression is reduced this is associated with BAV in humans.

Keywords : Bicuspid aortic valve Aggrecan Hemodynamic

Type de document :

Article dans une revue

International Journal of Cardiology, Elsevier, 2017, 249, pp.340 - 343. 〈10.1016/j.ijcard.2017.09.174〉

Domaine :

Sciences du Vivant [q-bio] / Médecine humaine et pathologie / Cardiologie et système cardiovasculaire

Liste complète des métadonnées

Littérature citée [16 références] Voir Masquer Télécharger

http://www.hal.inserm.fr/inserm-01617193
Contributeur : Adèle Faucherre <>
Soumis le : jeudi 29 mars 2018 - 10:04:07
Dernière modification le : lundi 27 août 2018 - 09:44:38
Document(s) archivé(s) le : jeudi 13 septembre 2018 - 12:07:25

RambeaudIntJCardiol2017.pdf

Fichiers produits par l'(les) auteur(s)

Reduced aggrecan expression affects cardiac outflow tract development in zebrafish and is associated with bicuspid aortic valve disease in humans

Fichier

Identifiants

Collections

Citation

Exporter

Métriques

252

17

Contact

Reduced aggrecan expression affects cardiac outflow tract development in zebrafish and is associated with bicuspid aortic valve disease in humans

Fichier

Identifiants

Collections

Citation

Exporter

Partager

Métriques

252

17

Contact