Structural abnormalities in the non-dilated ascending aortic wall of bicuspid aortic valve patients

Background: A bicuspid aortic valve (BAV) is the most common congenital cardiac malformation. The development of the aortic valve is closely related to the development of the ascending aorta, associated with structural differences in the bicuspid aorta. Here we describe the non-dilated ascending aortic wall in bicuspid aortic valve patients. Methods: BAV (n=41) and tricuspid aortic valve (TAV) (n=18) non-dilated ascending aortic wall samples were studied. We investigated the following features of the aortic wall: vessel wall thickness, endothelial cell morphology, atherosclerosis, and elastic lamellae organization. Medial pathologic features encompassing elastic fiber thinning, fragmentation and degeneration, overall medial degeneration, mucoid extracellular matrix accumulation, and smooth muscle cell nuclei loss were studied. Furthermore, we included apoptosis, periaortic inflammation, and the level of expression of differentiated vascular smooth muscle cells. Results: The non-dilated BAV ascending aortic wall is characterized by a significantly thinner intimal layer, without features of atherosclerosis (P<.001). The medial layer is significantly thicker (P<.001) with more mucoid extracellular matrix accumulation (P<.001). All other medial pathologic features were more prominent in the TAV (P<.001). The media has significantly less differentiated vascular smooth muscle cells (P<.001) between the neatly regulated elastic lamellae which are thinner in the BAV as compared to the TAV (P<.0001). Conclusions: The BAV ascending aorta without dilatation is characterized by a differentiation defect of vascular smooth muscle cells in the media and a significantly thinner intimal layer without overt pathologic features

Nitric oxide synthase-3 deficiency results in hypoplastic coronary arteries and postnatal myocardial infarction

Aims Hypoplastic coronary artery disease is a rare congenital abnormality that is associated with sudden cardiac death. However, molecular mechanisms responsible for this disease are not clear. The aim of the present study was to assess the role of nitric oxide synthase-3 (NOS3) in the pathogenesis of hypoplastic coronary arteries. Methods and results Wild-type (WT), NOS3 -/-, and a novel cardiac-specific NOS3 overexpression mouse model were employed. Deficiency in NOS3 resulted in coronary artery hypoplasia in foetal mice and spontaneous myocardial infarction in postnatal hearts. Coronary artery diameters, vessel density, and volume were significantly decreased in NOS3-/- mice at postnatal day 0. In addition, NOS3-/- mice showed a significant increase in the ventricular wall thickness, myocardial volume, and cardiomyocyte cell size compared with WT mice. Lack of NOS3 also down-regulated the expression of Gata4, Wilms tumour-1, vascular endothelial growth factor, basic fibroblast growth factor and erythropoietin, and inhibited migration of epicardial cells. These abnormalities and hypoplastic coronary arteries in the NOS3-/- mice were completely rescued by the cardiac-specific overexpression of NOS3. Conclusion Nitric oxide synthase-3 is required for coronary artery development and deficiency in NOS3 leads to hypoplastic coronary arteries. © 2014 The Author

Normal stages of embryonic development of a brood parasite, the rosy bitterling Rhodeus ocellatus (Teleostei: Cypriniformes).

Funder: China Scholarship Council; Id: http://dx.doi.org/10.13039/501100004543Bitterlings, a group of freshwater teleosts, provide a fascinating example among vertebrates of the evolution of brood parasitism. Their eggs are laid inside the gill chamber of their freshwater mussel hosts where they develop as brood parasites. Studies of the embryonic development of bitterlings are crucial in deciphering the evolution of their distinct early life-history. Here, we have studied 255 embryos and larvae of the rosy bitterling (Rhodeus ocellatus) using in vitro fertilization and X-ray microtomography (microCT). We describe 11 pre-hatching and 13 post-hatching developmental stages spanning the first 14 days of development, from fertilization to the free-swimming stage. In contrast to previous developmental studies of various bitterling species, the staging system we describe is character-based and therefore more compatible with the widely-used stages described for zebrafish. Our bitterling data provide new insights into to the polarity of the chorion, and into notochord vacuolization and yolk sac extension in relation to body straightening. This study represents the first application of microCT scanning to bitterling development and provides one of the most detailed systematic descriptions of development in any teleost. Our staging series will be an important tool for heterochrony analysis and other comparative studies of teleost development, and may provide insight into the co-evolution of brood parasitism

Echocardiographic Assessment of Embryonic and Fetal Mouse Heart Development: A Focus on Haemodynamics and Morphology

Background. Heart development is a complex process, and abnormal development may result in congenital heart disease (CHD). Currently, studies on animal models mainly focus on cardiac morphology and the availability of hemodynamic data, especially of the right heart half, is limited. Here we aimed to assess the morphological and hemodynamic parameters of normal developing mouse embryos/fetuses by using a high-frequency ultrasound system. Methods. A timed breeding program was initiated with a WT mouse line (Swiss/129Sv background). All recordings were performed transabdominally, in isoflurane sedated pregnant mice, in hearts of sequential developmental stages: 12.5, 14.5, and 17.5 days after conception (n=105). Results. Along development the heart rate increased significantly from 125 ± 9.5 to 219 ± 8.3 beats per minute. Reliable flow measurements could be performed across the developing mitral and tricuspid valves and outflow tract. M-mode measurements could be obtained of all cardiac compartments. An overall increase of cardiac systolic and diastolic function with embryonic/fetal development was observed. Conclusion. High-frequency echocardiography is a promising and useful imaging modality for structural and hemodynamic analysis of embryonic/fetal mouse hearts

Can transforming growth factor beta and downstream signalers distinguish bicuspid aortic valve patients susceptible for future aortic complications?

Patients with a bicuspid aortic valve have an extreme high risk to develop a thoracic aortic aneurysm and dissection (TAAD). TAADs form a leading cause of death worldwide, with the majority of deaths being preventable if individuals at risk are identified and properly managed. Risk stratification for TAADs in bicuspidy is so far solely based on the aortic diameter. Exclusive use of aortic wall dimension, as in the current guidelines, is however not sufficient in selecting patients vulnerable for future aortic wall complications. Moreover, there are no effective medical treatments for TAADs to retain progressive aortic dilatation and thus prevent or delay aortic complications. Only surgical replacement of the aorta increases life expectancy in patients with a risk for a TAAD. Therefore, the next major challenge in the management of TAADs is the development of a personalized patient-tailored risk stratification for early detection of patients with an increased risk for TAADs, who will benefit from surgical resection of the aorta. Several signaling pathways have been studied in recent times to develop a patient specific risk stratification model. In this paper we discuss TGF-β signaling and downstream signalers as potential markers for future aortic complications in bicuspid aortic valve patients

Can transforming growth factor beta and downstream signalers distinguish bicuspid aortic valve patients susceptible for future aortic complications?

Patients with a bicuspid aortic valve have an extreme high risk to develop a thoracic aortic aneurysm and dissection (TAAD). TAADs form a leading cause of death worldwide, with the majority of deaths being preventable if individuals at risk are identified and properly managed. Risk stratification for TAADs in bicuspidy is so far solely based on the aortic diameter. Exclusive use of aortic wall dimension, as in the current guidelines, is however not sufficient in selecting patients vulnerable for future aortic wall complications. Moreover, there are no effective medical treatments for TAADs to retain progressive aortic dilatation and thus prevent or delay aortic complications. Only surgical replacement of the aorta increases life expectancy in patients with a risk for a TAAD. Therefore, the next major challenge in the management of TAADs is the development of a personalized patient-tailored risk stratification for early detection of patients with an increased risk for TAADs, who will benefit from surgical resection of the aorta. Several signaling pathways have been studied in recent times to develop a patient specific risk stratification model. In this paper we discuss TGF-β signaling and downstream signalers as potential markers for future aortic complications in bicuspid aortic valve patients

Can general histopathology distinguish bicuspid aortopathy?

Cardiolog