Origin of congenital coronary arterio-ventricular fistulae from anomalous epicardial and myocardial development

Coronary Artery Fistulae (CAFs) are cardiac congenital anomalies consisting of an abnormal communication of a coronary artery with either a cardiac chamber or another cardiac vessel. In humans, these congenital anomalies can lead to complications such as myocardial hypertrophy, endocarditis, heart dilatation, and failure. Unfortunately, despite their clinical relevance, the aetiology of CAFs remains unknown. In this work, we have used two different species (mouse and avian embryos) to experimentally model CAFs morphogenesis. Both conditional Itga4 (alpha 4 integrin) epicardial deletion in mice and cryocauterisation of chick embryonic hearts disrupted epicardial development and ventricular wall growth, two essential events in coronary embryogenesis. Our results suggest that myocardial discontinuities in the embryonic ventricular wall 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. The structure of these CAF-like anomalies was compared with histopathological data from a human CAF. Our results provide relevant information for the early diagnosis of these congenital anomalies and the molecular mechanisms that regulate their embryogenesis. Cardiology: How heart development goes astrayInsights from animal models highlight specific disturbances in early heart development as a likely point of origin for the formation of coronary artery fistulas (CAF), abnormal linkages between one of the coronary arteries and other regions of the heart. Children born with such defects are at heightened risk of serious heart problems. Using chick and mouse embryos, Jose Perez-Pomares at the University of Malaga in Spain revealed a mechanism by which CAFs may arise in humans. Early in development, the heart muscle that forms the ventricle chambers undergoes a process of growth and compaction that transforms ventricular walls into thick and dense tissue layers. The researchers demonstrated that genetic or physical disruptions that interfere with this process give rise to CAF-like features, highlighting a promising strategy for modelling this congenital defect.

Automated summary

Coronary Artery Fistulae (CAFs) are cardiac congenital anomalies characterized by abnormal communication between a coronary artery and a heart chamber or vessel. The cause of CAFs is still unknown. Using mouse and avian embryos as models, researchers have found that disruptions in epicardial development and ventricular wall growth lead to the formation of abnormal coronary-like structures in direct connection with the ventricular lumen. These findings provide insights into the early diagnosis and molecular mechanisms of CAFs.