Normal and abnormal development of the aortic valve and ascending aortic wall: a comprehensive overview of the embryology and pathology of the bicuspid aortic valve.

A bicuspid aortic valve (BAV) is the most prevalent congenital cardiac anomaly, in which the valve has only two leaflets, instead of the normal three. Patients with a BAV have an increased risk of aneurysm formation and the development of an aortic dissection. Vascular smooth muscle cells in both the non- and dilated aortic wall are characterized by a maturation defect in all BAV patients, as compared to patients with a tricuspid aortic valve, which can contribute to inherent developmental susceptibility.

Ventricular Septation and Outflow Tract Development in Crocodilians Result in Two Aortas with Bicuspid Semilunar Valves.

: 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.

Extent of Coronary Artery Disease in Patients With Stenotic Bicuspid Versus Tricuspid Aortic Valves.

Background Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, which is often complicated by aortic valve stenosis (AoS). In tricuspid aortic valve (TAV), AoS strongly associates with coronary artery disease (CAD) with common pathophysiological factors. Yet, it remains unclear whether AoS in patients with BAV is also associated with CAD.

The Leiden Convention coronary coding system: translation from the surgical to the universal view.

Aims: The Leiden Convention coronary coding system structures the large variety of coronary anatomical patterns; isolated and in congenital heart disease. It is widely used by surgeons but not by cardiologists as the system uses a surgeons' cranial view. Since thoracic surgeons and cardiologists work closely together, a coronary coding system practical for both disciplines is mandatory.

A Systematic Histopathologic Evaluation of Type-A Aortic Dissections Implies a Uniform Multiple-Hit Causation.

(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 ( = 58, mean age 63 years) with TAAD were collected.

Disturbed nitric oxide signalling gives rise to congenital bicuspid aortic valve and aortopathy.

Patients with a congenital bicuspid aortic valve (BAV), a valve with two instead of three aortic leaflets, have an increased risk of developing thoracic aneurysms and aortic dissection. The mechanisms underlying BAV-associated aortopathy are poorly understood. This study examined BAV-associated aortopathy in mice, a model with congenital BAV formation.

Transforming Growth Factor Beta3 is Required for Cardiovascular Development.

Transforming growth factor beta3 () 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 , its overarching role remains unclear in cardiovascular development and disease. We used histological, immunohistochemical, and molecular analyses of fetuses and compared them to wildtype littermate controls.

Pulmonary ductal coarctation and left pulmonary artery interruption; pathology and role of neural crest and second heart field during development.

Objectives: In congenital heart malformations with pulmonary stenosis to atresia an abnormal lateral ductus arteriosus to left pulmonary artery connection can lead to a localised narrowing (pulmonary ductal coarctation) or even interruption We investigated embryonic remodelling and pathogenesis of this area.

Material And Methods: Normal development was studied in WntCre reporter mice (E10.0-12.

Human epicardium-derived cells reinforce cardiac sympathetic innervation.

Rationale: After cardiac damage, excessive neurite outgrowth (sympathetic hyperinnervation) can occur, which is related to ventricular arrhythmias/sudden cardiac death. Post-damage reactivation of epicardium causes epicardium-derived cells (EPDCs) to acquire a mesenchymal character, contributing to cardiac regeneration. Whether EPDCs also contribute to cardiac re/hyperinnervation, is unknown.

The Development of the Ascending Aortic Wall in Tricuspid and Bicuspid Aortic Valve: A Process from Maturation to Degeneration.

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.

Development and evolution of the metazoan heart.

The mechanisms of the evolution and development of the heart in metazoans are highlighted, starting with the evolutionary origin of the contractile cell, supposedly the precursor of cardiomyocytes. The last eukaryotic common ancestor is likely a combination of several cellular organisms containing their specific metabolic pathways and genetic signaling networks. During evolution, these tool kits diversified.

The role of hemodynamics in bicuspid aortopathy: a histopathologic study.

Background: A bicuspid aortic valve (BAV) is the most common congenital cardiac malformation and is associated with ascending aortic dilation in 60%-80% of patients. In this study, we aimed to address the role of hemodynamic influences on the development of aortopathy in BAV patients.

Patient And Methods: BAV (n=36) and tricuspid aortic valve (TAV) patients (n=17) undergoing aortic valve replacement underwent preoperative flow magnetic resonance imaging (MRI) assessment to detect the area of maximal flow-induced stress in the proximal aorta.

Disruption of RHOA-ROCK Signaling Results in Atrioventricular Block and Disturbed Development of the Putative Atrioventricular Node.

The RHOA-ROCK signaling pathway is involved in numerous developmental processes, including cell proliferation, differentiation and migration. RHOA is expressed in the atrioventricular node (AVN) and altered expression of RHOA results in atrioventricular (AV) conduction disorders in mice. The current study aims to detect functional AVN disorders after disturbing RHOA-ROCK signaling in chicken embryos.

Hemodynamics in Cardiac Development.

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.

Coding of coronary arterial origin and branching in congenital heart disease: The modified Leiden Convention.

Objectives: Variations in coronary anatomy are common and may relate to the position of the coronary ostium relative to the aortic sinus, the angle of coronary take-off, or the course of the coronary arterial branches. Several classification systems have been proposed. However, they all lack a simple rationale that is applicable irrespective of the relative position of the great arteries, as well as in bicuspid aortic valves.

Bicuspid aortic valve formation: mutation leads to abnormal lineage patterning of neural crest cells and the second heart field.

The bicuspid aortic valve (BAV), a valve with two instead of three aortic leaflets, belongs to the most prevalent congenital heart diseases in the world, occurring in 0.5-2% of the general population. We aimed to understand how changes in early cellular contributions result in BAV formation and impact cardiovascular outflow tract development.

Pathogenesis of aortic wall complications in Marfan syndrome.

Background: Patients with Marfan (MFS) syndrome and patients with a bicuspid aortic valve (BAV) are more prone to develop aortic dilation and dissection compared to persons with a tricuspid aortic valve (TAV). To elucidate potential common as well as distinct pathways of clinical relevance, we compared the histopathological substrates of aortic pathology.

Patient And Methods: Ascending aortic wall specimen were divided in five groups: BAV (n=36) and TAV (n=23) without and with dilation and non-dilated MFS (n=8).

Pulmonary Valve Morphology in Patients with Bicuspid Aortic Valves.

The aortic and pulmonary valve share a common developmental origin from the embryonic arterial trunk. Bicuspid aortic valve is the most common congenital anomaly and can occur isolated as well as in association with other congenital heart disease (CHD). Data on pulmonary valve morphology in these cases are scarce.

RHOA-ROCK signalling is necessary for lateralization and differentiation of the developing sinoatrial node.

Aims: RHOA-ROCK signalling regulates cell migration, proliferation, differentiation, and transcription. RHOA is expressed in the developing cardiac conduction system in chicken and mice. In early development, the entire sinus venosus myocardium, including both the transient left-sided and the definitive sinoatrial node (SAN), has pacemaker potential.

Outflow tract septation and the aortic arch system in reptiles: lessons for understanding the mammalian heart.

Background: Cardiac outflow tract patterning and cell contribution are studied using an evo-devo approach to reveal insight into the development of aorto-pulmonary septation.

Results: We studied embryonic stages of reptile hearts (lizard, turtle and crocodile) and compared these to avian and mammalian development. Immunohistochemistry allowed us to indicate where the essential cell components in the outflow tract and aortic sac were deployed, more specifically endocardial, neural crest and second heart field cells.

Genome-wide methylation analysis identifies novel CpG loci for perimembranous ventricular septal defects in human.

Aim: Congenital heart diseases are the most common birth defects worldwide and leading cause of infant mortality. The perimembranous ventricular septal defect is most prevalent. Epigenetics may provide an underlying mechanism of the gene-environment interactions involved.

Comparative transcriptomic analysis identifies genes differentially expressed in human epicardial progenitors and hiPSC-derived cardiac progenitors.

Regenerative therapies hold great potential to change the treatment paradigm for cardiac diseases. Human cardiac progenitor cells can be used for drug discovery in this area and also provide a renewable source of cardiomyocytes. However, a better understanding of their characteristics is critical for interpreting data obtained from drug screening using these cells.