| Autor: |
P Palmquist-Gomes, A Ruiz-Villalba, JA Guadix, JP Romero, B Bessiéres, D MacGrogan, L Conejo, A Ortiz, B Picazo, L Houyel, D Gómez-Cabrero, SM Meilhac, JL de la Pompa, JM Pérez-Pomares |
| Přispěvatelé: |
Universidad de Málaga [Málaga] = University of Málaga [Málaga], The Andalusian Center for Nanomedicine and Biotechnology (BIONAND), Morphogenèse du cœur - Heart morphogenesis (Imagine - Institut Pasteur U1163), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Instituto de Salud Carlos III [Madrid] (ISC), Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares [Spain] (CIBERCV), Instituto de Investigación Biomédica de Málaga [Malaga, Espagne] (IBIMA), King Abdullah University of Science and Technology (KAUST), This work was supported by Spanish Ministry of Science, R+D+i National Programme [grant number RTI2018-095410-RB-I00], Spanish Ministry of Science-ISCIII [grant number RD16/0011/0030], and University of Málaga [grant number UMA18-FEDERJA-146] to [JMPP], Consejería de Salud y Familias, Junta de Andalucía [grant number PIER-0084-2019] to [JAGD], University of Málaga [grant number I Plan Propio-UMA-A.4] to [ARV], Spanish Ministry of Science, Innovation and Universities (MCIU) (CIBER CV) [grant numbers PID2019-104776RB-I00 and CB16/11/00399] to [JLDLP]. |
| Rok vydání: |
2022 |
| Předmět: |
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| Popis: |
AimsIn this work we investigated the embryonic origin of coronary arterio-ventricular connections, known as coronary artery fistulas (CAF), a congenital heart disease associated to postnatal and adult changes in systemic hemodynamics that may cause cardiac ischemia.Methods and resultswe have used different animal models (mouse and avian embryos) to experimentally model CAF morphogenesis. Conditional Itga4 (alpha 4 integrin) epicardial deletion in mice and cryocauterisation of chick and quail embryonic hearts disrupted epicardial development and ventricular wall growth, two essential events in coronary embryogenesis. Additional transcriptomics and in vitro analyses were performed to better understand how arterio-ventricular connections are originated in the embryonic heart. Our results show myocardial discontinuities in the developing heart of mutant mice presenting epicardial defects and avian embryos submitted to a physical cryodamage of the ventricle. These ventricular discontinuities promote the formation of endocardial pouch-like structures resembling human CAF. The structure of these CAF-like anomalies was compared with histopathological data from a human CAF, showing histomorphological and immunochemical similarities. Both human and mutant mouse hearts showed similar anomalies in the compaction of the ventricular myocardium. In vitro experiments showed the abnormal contact between the epicardium and the endocardium promote the precocious differentiation of epicardial cells to smooth muscle.ConclusionOur work suggests that myocardial discontinuities in the embryonic ventricular wall are a causative of CAF. These discontinuities would promote the early contact of the endocardium with epicardial-derived coronary progenitors at the cardiac surface, leading to ventricular endocardial extrusion, precocious differentiation of coronary smooth muscle cells, and the formation of pouch-like aberrant coronary-like structures in direct connection with the ventricular lumen.Translational perspectiveCongenital coronary artery fistulas (CAFs) lead to complications such as myocardial hypertrophy, endocarditis, heart dilatation and failure. Unfortunately, and despite their clinical relevance, the origins these congenital anomalies remain unknown. In this work, we provide information on the developmental mechanisms involved in the formation of CAFs that is relevant for their early diagnosis and prevention. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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