Academic Journal
Endocardial-to-mesenchymal transition underlies cardiac outflow tract septation and bicuspid aortic valve formation in the Syrian hamster model
| Title: | Endocardial-to-mesenchymal transition underlies cardiac outflow tract septation and bicuspid aortic valve formation in the Syrian hamster model |
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| Authors: | María Teresa Soto-Navarrete, Bárbara Pozo-Vilumbrales, Miguel Á. López-Unzu, Laura Martín-Chaves, Ana C. Durán, Borja Fernández |
| Source: | Scientific Reports, Vol 15, Iss 1, Pp 1-14 (2025) |
| Publisher Information: | Nature Portfolio, 2025. |
| Publication Year: | 2025 |
| Collection: | LCC:Medicine LCC:Science |
| Subject Terms: | Bicuspid aortic valve, Cardiac outflow tract, Endocardial cushion fusion, Endocardial-mesenchymal transition, Hamster embryo, Medicine, Science |
| More Details: | Abstract 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-025-91454-6 |
| Access URL: | https://doaj.org/article/af00c68462564f76b911164ec6798098 |
| Accession Number: | edsdoj.f00c68462564f76b911164ec6798098 |
| Database: | Directory of Open Access Journals |
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| ISSN: | 20452322 |
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| DOI: | 10.1038/s41598-025-91454-6 |
| Published in: | Scientific Reports |
| Language: | English |