Search Results (5)

Background: The outflow tract of crocodilians resembles that of birds and mammals as ventricular septation is complete. The arterial anatomy, however, presents with a pulmonary trunk originating from the right ventricular cavum, and two aortas originating from either the right or left ventricular cavity. Mixing of blood in crocodilians cannot occur at the ventricular level as in other reptiles but instead takes place at the aortic root level by a shunt, the foramen of Panizza, the opening of which is guarded by two facing semilunar leaflets of both bicuspid aortic valves. Methods: Developmental stages of Alligator mississipiensis, Crocodilus niloticus and Caiman latirostris were studied histologically. Results and Conclusions: The outflow tract septation complex can be divided into two components. The aorto-pulmonary septum divides the pulmonary trunk from both aortas, whereas the interaortic septum divides the systemic from the visceral aorta. Neural crest cells are most likely involved in the formation of both components. Remodeling of the endocardial cushions and both septa results in the formation of bicuspid valves in all three arterial trunks. The foramen of Panizza originates intracardially as a channel in the septal endocardial cushion. Full article

(1) Background: The pathophysiologic basis of an acute type A aortic dissection (TAAD) is largely unknown. In an effort to evaluate vessel wall defects, we systematically studied aortic specimens in TAAD patients. (2) Methods: Ascending aortic wall specimens (n = 58, mean age 63 years) with TAAD were collected. Autopsy tissues (n = 17, mean age 63 years) served as controls. All sections were studied histopathologically. (3) Results: Pathomorphology in TAAD showed predominantly moderate elastic fiber fragmentation/loss, elastic fiber thinning, elastic fiber degeneration, mucoid extracellular matrix accumulation, smooth muscle cell nuclei loss, and overall medial degeneration. The control group showed significantly fewer signs of those histopathological features (none-mild, p = 0.00). It was concluded that the dissection plane consistently coincides with the vasa vasorum network, and that TAAD associates with a significantly thinner intimal layer p = 0.005). (4) Conclusions: On the basis of the systematic evaluation and the consistent presence of diffuse, pre-existing medial defects, we hypothesize that TAAD relates to a developmental defect of the ascending aorta and is caused by a triple-hit mechanism that involves (I) an intimal tear; and (II) a diseased media, which allows (III) propagation of the tear towards the plane of the vasa vasorum where the dissection further progresses. Full article

Transforming growth factor beta3 (TGFB3) gene mutations in patients of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD1) and Loeys-Dietz syndrome-5 (LDS5)/Rienhoff syndrome are associated with cardiomyopathy, cardiac arrhythmia, cardiac fibrosis, cleft palate, aortic aneurysms, and valvular heart disease. Although the developing heart of embryos express Tgfb3, its overarching role remains unclear in cardiovascular development and disease. We used histological, immunohistochemical, and molecular analyses of Tgfb3^−/− fetuses and compared them to wildtype littermate controls. The cardiovascular phenotypes were diverse with approximately two thirds of the Tgfb3^−/− fetuses having one or more cardiovascular malformations, including abnormal ventricular myocardium (particularly of the right ventricle), outflow tract septal and alignment defects, abnormal aortic and pulmonary trunk walls, and thickening of semilunar and/or atrioventricular valves. Ventricular septal defects (VSD) including the perimembranous VSDs were observed in Tgfb3^−/− fetuses with myocardial defects often accompanied by the muscular type VSD. In vitro studies using TGFβ3-deficient fibroblasts in 3-D collagen lattice formation assays indicated that TGFβ3 was required for collagen matrix reorganization. Biochemical studies indicated the ‘paradoxically’ increased activation of canonical (SMAD-dependent) and noncanonical (MAP kinase-dependent) pathways. TGFβ3 is required for cardiovascular development to maintain a balance of canonical and noncanonical TGFβ signaling pathways. Full article

Background: Patients with a bicuspid aortic valve (BAV) have an increased risk for aortic dilation and dissection. In this study, we provide a histological stratification of the developing aorta in the tricuspid aortic valve (TAV) and the BAV populations as a reference for future studies on aortopathy and related syndromes. Methods: Non-dilated TAV and BAV ascending aortic wall samples were collected, including 60 TAV (embryonic–70 years) and 32 BAV specimens (fetal–72 years, categorized in eight age groups. Results: In TAV, intimal development starts in the neonatal phase. After birth, the thickness of the medial layer increases significantly by increase of elastic lamellae up to and including the “young child” phase stabilizing afterwards. The BAV shows already prenatal intimal thickening becoming significantly thinner after birth subsequently stabilizing. In BAV, increase in elastic lamellae is seen between the young child and the adolescent phases, stabilizing afterwards. Conclusions: Vascular development in TAV is described in three phases: maturation, stabilization, and degeneration. For BAV, the development can be described in two phases: maturation (already prenatally) and degeneration. After birth, the development of the aorta is characterized by degeneration, leading to weakening of the ascending aortic wall and increasing the risk of aortopathy. Full article

The beating heart is subject to intrinsic mechanical factors, exerted by contraction of the myocardium (stretch and strain) and fluid forces of the enclosed blood (wall shear stress). The earliest contractions of the heart occur already in the 10-somite stage in the tubular as yet unsegmented heart. With development, the looping heart becomes asymmetric providing varying diameters and curvatures resulting in unequal flow profiles. These flow profiles exert various wall shear stresses and as a consequence different expression patterns of shear responsive genes. In this paper we investigate the morphological alterations of the heart after changing the blood flow by ligation of the right vitelline vein in a model chicken embryo and analyze the extended expression in the endocardial cushions of the shear responsive gene Tgfbeta receptor III. A major phenomenon is the diminished endocardial-mesenchymal transition resulting in hypoplastic (even absence of) atrioventricular and outflow tract endocardial cushions, which might be lethal in early phases. The surviving embryos exhibit several cardiac malformations including ventricular septal defects and malformed semilunar valves related to abnormal development of the aortopulmonary septal complex and the enclosed neural crest cells. We discuss the results in the light of the interactions between several shear stress responsive signaling pathways including an extended review of the involved Vegf, Notch, Pdgf, Klf2, eNos, Endothelin and Tgfβ/Bmp/Smad networks. Full article