2026-05-17T00:18:37Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/268212025-12-18T13:01:54Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Soto-Navarrete, María Teresa
author
Pozo-Vilumbrales, Bárbara
author
López-Unzu, Miguel Á
author
Martín-Chaves, Laura
author
Durán, Ana C
author
Fernández, Borja
funder
Ministerio de Ciencia e Innovación (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
2025-07-10T10:49:29Z
2025-07-10T10:49:29Z
2025-03-12
Sci Rep. 2025 Mar 12;15(1):8583.
Scientific Reports
40074779
https://hdl.handle.net/20.500.12105/26821
Right-left bicuspid aortic valve (R-L BAV) is the most frequent phenotype of the most common congenital heart disease. Its etiology is based on two associated morphogenetic defects during cardiac outflow tract (OFT) septation: abnormal migration of cardiac neural crest (CNC) cells, and excessive fusion of the conal ridges (CRs). The aim of this study is to elucidate the mechanism involved in the fusion of the CRs responsible for normal and abnormal OFT septation and BAV formation. Two mechanisms have been proposed: endocardial apoptosis and endocardial-mesenchymal transition (EMT). The involvement of these mechanisms in the fusion event was tested in embryos of the hamster model with BAV. Apoptotic cells were absent in the fusion area of the CRs. However, we detected endocardial cells (CD34;VE-Cadherin) showing positive signals for migration markers (α-actin) in the fusion area of the CRs of embryos developing both normal aortic valve and BAV. These cells showed an intermediate morphological phenotype between endocardial and mesenchymal cells. The findings clearly indicate that EMT, and not apoptosis, is the cellular mechanism underlying the normal and excessive fusion of CRs that give rise to tricuspid aortic valve and BAV, respectively. Furthermore, our results show that the fusion of CRs in embryos developing BAV continues after the OFT septation, suggesting over-induction of EMT by abnormally distributed CNC cells.
eng
Bicuspid aortic valve
Cardiac outflow tract
Endocardial cushion fusion
Endocardial-mesenchymal transition
Hamster embryo
Endocardial-to-mesenchymal transition underlies cardiac outflow tract septation and bicuspid aortic valve formation in the Syrian hamster model.
research article
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
URL
https://repisalud.isciii.es/bitstreams/3c0e3ccf-a9bc-48ac-9ab4-3e3f466252ab/download
File
MD5
d0177e07da0099b84d35012ffcb193c4
9713317
application/pdf
Endocardial_to_mesenchymal_Sci Rep_2025.pdf