High take-off (HTO) is a rare congenital coronary artery anomaly associated with sudden cardiac death. The coronary ostium is located in the ascending aorta above the sinotubular junction. The morphogenetic defect leading to HTO is currently unknown. Our group has shown occurrence of HTO in different strains of laboratory mice, including C57Bl/6 strain with 58% incidence of HTO and Balb/c strain with null incidence.
Our aim is to investigate the aetiology of HTO, using C57BL/6 and Balb/c mice strains as experimental models. The process of coronariogenesis was examined in E13.5 and E14.5 mouse embryos of C57Bl/6 (n=27) and Balb/c (n=23) strains. We used histochemistry and immunohistochemistry with specific markers for the vascular plexuses involved in the formation of coronary arteries (PROX1 and ERG 1/2/3).
In the mouse embryo, coronary ostia develop at approximately stage E14.5. The location of the ostia is determined by the confluence of two vascular plexuses. The transient lymphatic subepicardial aortic plexus migrates from the pharyngeal region, invading the subepicardial space of the intrapericardial thoracic arteries at around E13.5. The primary or ventricular plexus, which constitutes the future coronary vascular network, forms in situ, reaching the embryonic cardiac outflow tract at around E14. Eighteen of the 27 (66.7%) C57Bl/6 embryos showed an exacerbated subepicardial aortic plexus compared to the 23 Balb/c embryos, in which the subepicardial aortic plexus exhibited a normal size. These results suggest that the embryonic origin of HTO could be due to a defect in the growth of the subepicardial aortic plexus, resulting in an exacerbated vessel network. This overgrowth seems to alter the invasion and connection of the primary plexus to the aortic root for the establishment of the ostia and coronary trunks. From a biomedical viewpoint, it would be of great interest to investigate the molecular mechanisms underlying the overgrowth of the aortic plexus.
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