Endocardial Fibroelastosis is Secondary to Hemodynamic Alterations in the Chick Embryonic Model of Hypoplastic Left Heart Syndrome

Pesevski, Zivorad; Kvasilová, Alena; Stopkova, Tereza; Naňka, Ondřej; Krejčí, Eliška; Buffinton, Christine Miller; Kočková, Radka; Eckhardt, Adam; Sedmera, David

doi:10.1002/dvdy.24521

Cited by 28 publications

(29 citation statements)

References 43 publications

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“…In addition optical methods have been applied to demonstrate flow patterns in chicken and zebrafish [21,24]. Therefore, it is likely that interfering with hemodynamic load, by either decreasing or increasing blood pressure and flow velocities, usually result in cardiac malformations that are quite comparable albeit with varying incidence and severity [45,46,47]. Ligation of a vitelline vein or the left atrium (decrease) or OFT banding (increase) all interfered with looping, ventricular septation and valve formation, but also aortic arch artery morphogenesis [48].…”

Section: Discussionmentioning

confidence: 99%

Hemodynamics in Cardiac Development

Poelmann

Groot

2018

JCDD

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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.

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Section: Discussionmentioning

confidence: 99%

Hemodynamics in Cardiac Development

Poelmann

Groot

2018

JCDD

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“…Progressive LV hypoplasia also occurs in the human fetus with aortic valve stenosis and hypoplastic left heart syndrome (HLHS) [ 184 , 185 ]. The embryonic chick LV after LAL displays disordered gene expression as well as endocardial fibroelastosis [ 186 , 187 ], which may be due, in part, to shear sensing by endocardial cilia [ 188 ]. The human heart displays altered gene expression in the setting of HLHS [ 189 , 190 , 191 ], though it is not clear if those changes in gene expression are causative or adaptive.…”

Section: Chronic Interventional Models Investigate the Relationshimentioning

confidence: 99%

Validating the Paradigm That Biomechanical Forces Regulate Embryonic Cardiovascular Morphogenesis and Are Fundamental in the Etiology of Congenital Heart Disease

Keller

Kowalski

Tinney

et al. 2020

JCDD

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The goal of this review is to provide a broad overview of the biomechanical maturation and regulation of vertebrate cardiovascular (CV) morphogenesis and the evidence for mechanistic relationships between function and form relevant to the origins of congenital heart disease (CHD). The embryonic heart has been investigated for over a century, initially focusing on the chick embryo due to the opportunity to isolate and investigate myocardial electromechanical maturation, the ability to directly instrument and measure normal cardiac function, intervene to alter ventricular loading conditions, and then investigate changes in functional and structural maturation to deduce mechanism. The paradigm of “Develop and validate quantitative techniques, describe normal, perturb the system, describe abnormal, then deduce mechanisms” was taught to many young investigators by Dr. Edward B. Clark and then validated by a rapidly expanding number of teams dedicated to investigate CV morphogenesis, structure–function relationships, and pathogenic mechanisms of CHD. Pioneering studies using the chick embryo model rapidly expanded into a broad range of model systems, particularly the mouse and zebrafish, to investigate the interdependent genetic and biomechanical regulation of CV morphogenesis. Several central morphogenic themes have emerged. First, CV morphogenesis is inherently dependent upon the biomechanical forces that influence cell and tissue growth and remodeling. Second, embryonic CV systems dynamically adapt to changes in biomechanical loading conditions similar to mature systems. Third, biomechanical loading conditions dynamically impact and are regulated by genetic morphogenic systems. Fourth, advanced imaging techniques coupled with computational modeling provide novel insights to validate regulatory mechanisms. Finally, insights regarding the genetic and biomechanical regulation of CV morphogenesis and adaptation are relevant to current regenerative strategies for patients with CHD.

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“…If the developing tissue becomes too hypoxic, however, it can lead to defects. Many studies support that hypoxia leads to an increase in fibre due to increased expression of extracellular matrix proteins [72,73].…”

Section: Hypoplastic Left Heart Syndromementioning

confidence: 99%

“…There is speculation, however, about the order in which the defects develop. Most literature supports that it is altered haemodynamics that lead to hypoxia that leads to fibrosis but it is possible that there are other causes of the fibrosis [73].…”

Section: Hypoplastic Left Heart Syndromementioning

confidence: 99%

Avian Cardiovascular Disease Characteristics, Causes and Genomics

Kubale¹,

Merry²,

Miller³

et al. 2018

Application of Genetics and Genomics in Poultry Science

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Cardiovascular disease is common in avian species and increasing commercial economic losses and demand for healthcare in the household/smallholding veterinary sector has resulted in increased research into these disorders. This in turn has highlighted the importance of breeding, genetic testing and possibilities for future prognostic and diagnostic testing. Research into avian cardiovascular genetics has rapidly accelerated. Previously much work was undertaken in mammals with information extrapolated and transferred to birds. Birds have also been used to model cardiovascular disease and therefore knowledge has become enriched due to this endeavour. Increasingly, the avian genome is being analysed in its own right. This work is assisted by the growing number of avian genomes being published. In 2015, Nature published news on the 'Bird 10K' project, which aims to sequence 10,500 extant bird species. By 2018, the Avian Genomes Consortium had published the sequences of 45 species/34 orders. This review investigates a range of avian cardiovascular disorders in order to highlight their pathologies, epidemiology and genetics in addition to avian models of heart disease. With the availability of more reference genomes, increases in the number and magnitude of avian studies and more advanced technologies, the genetics behind avian cardiovascular disorders is being unravelled.

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Endocardial Fibroelastosis is Secondary to Hemodynamic Alterations in the Chick Embryonic Model of Hypoplastic Left Heart Syndrome

Cited by 28 publications

References 43 publications

Hemodynamics in Cardiac Development

Hemodynamics in Cardiac Development

Validating the Paradigm That Biomechanical Forces Regulate Embryonic Cardiovascular Morphogenesis and Are Fundamental in the Etiology of Congenital Heart Disease

Avian Cardiovascular Disease Characteristics, Causes and Genomics

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