Dissertations / Theses on the topic 'Heart development'
To see the other types of publications on this topic, follow the link: Heart development.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Heart development.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Brown, Jessie Ann. "RUNX2 in Embryonic Heart Development and Heart Disease." Thesis, The University of Arizona, 2011. http://hdl.handle.net/10150/144250.
Full text
2
Kim, WooJin. "Endothelial furin and heart development." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=87012.
Full textAbstract:
In mammals, seven proprotein convertases (PCs) cleave secretory proteins after basic residues. Four members of this family are called furin-like PCs: furin, PACE4, PC5, and PC7. Furin and PC7 are ubiquitous, while PACE4 and PC5 are widely expressed. In vitro, they share many substrates (redundancy). However, furin is essential during development. Inactivation of its gene (Pcsk3) in mouse resulted in lethality at embryonic day 11 (E11). The embryos exhibit multiple developmental defects, particularly related to the function of endothelial cells. In order to define the role of furin in endothelial cells, Pcsk3flox/flox mice carrying Tie2-Cre transgene that expresses Cre under the control of the Tie2 promoter were generated. Pcsk3flox/flox Tg(Tie2-cre) embryos (ecKO) do not survive, indicating that furin has an essential role in endothelial cells. We determined that lethality occurs after birth, and newborns have no visible phenotypes. However, magnetic resonance imaging revealed that ecKO mice exhibit a heart phenotype consisting of ventricular septal defects (VSD) and/or valve malformations.Searching for candidate furin substrates, the loss of which exhibit VSD led us to analyze the processing of endothelin-1 (ET-1) and bone morphogenic protein 4 (BMP4). While proET-1 cleavage into ET-1 is reduced by 57% in absence of furin in ecKO lungs, proBMP4 activation into BMP4 was more than 90% lost in the heart of these mice. We conclude that proET-1 and proBMP-4 are in vivo substrates of furin and that the impaired processing of proBMP-4 is most likely the cause of the observed VSD in mice lacking endothelial furin. Further studies on other regulatory proteins of endothelial cell will unravel more specific in vivo functions of furin identifying other in vivo substrates.
Chez les mammifères, 7 proprotéines convertases (PC) clivent diverses protéines de sécrétion après les acides aminés basiques. Quatre membres de cette famille de convertases sont appelés: furin, PACE4, PC5 et PC7. Furin et PC7 sont omniprésents, tandis que PACE4 et PC5 sont largement exprimées. In vitro, ils ont beaucoup de substrats en commun. Cependant, la furin est essentielle pendant le développement. L'inactivation de son gène (Pcsk3) dans la souris a abouti à la mortalité embryonnaire au 11éme jour (E11). Les embryons montrent de multiples défauts liés au développement particulièrement reliés à la fonction des cellules endothéliales. Afin de définir le rôle de la furin dans les cellules endothéliales, des souris Pcsk3flox/flox portant le transgène Tie2-Cre qui exprime Cre dans le contrôle du promoteur Tie2 ont été produites. Les embryons Pcsk3flox/flox Tg(Tie2-cre) (aussi référés comme ecKO) ne survivent pas, indiquant que la furin a un rôle essentiel dans les cellules endothéliales. Nous avons déterminé que la mortalité arrive peu de temps après la naissance, ne montrant aucun phénotype apparent. Cependant, l'imagerie par résonance magnétique a révélé que les souris ecKO présentent un défaut septal ventriculaire (VSD).
Par la sélection du phénotype utilisant VSD sur les substrats de la furin, nous avons observé que proendothelin-1 (proET-1) a été moins produite dans le poumon de souris ecKO. Nous avons aussi démontré que la protéine morphogénétique-4 de l'os (proBMP-4) a été aussi moins clivée dans le coeur de souris ecKO. Ces observations soutiennent notre hypothèse que proET-1 et proBMP-4 sont les substrats in vivo de la furin et que la production altérée de proBMP-4 est la cause de VSD la plus probable. De nouvelles études sur d'autres protéines régulatrices des cellules endothéliales élucideront les fonctions in vivo plus spécifiques de la furin et l'identification d'autres substrats in vivo. fr
3
Weinberger, Michael. "Epicardial heterogeneity during zebrafish heart development." Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:3f26b933-5f17-4fe3-bd86-9211af69a558.
Full textAbstract:
The epicardium, a cell layer enveloping the heart muscle, drives embryonic heart development and heart repair in the adult zebrafish. Previous studies found the epicardium to consist of multiple cell populations with distinct phenotypes and functions. Here, I investigated epicardial heterogeneity in the developing zebrafish heart, focusing on the developmental gene program that is also reactivated during adult heart regeneration. Transcription factor 21 (Tcf21), T-box 18 (Tbx18) and Wilms' tumor suppressor 1b (Wt1b) are often used interchangeably to identify the zebrafish epicardium. Analyzing newly generated reporter lines and endogenous gene expression, I showed that the epicardial expression of tcf21, tbx18 and wt1b during development is heterogeneous. I then collected epicardial cells from newly generated reporter lines at 5 days-post-fertilization and performed single-cell RNA sequencing. I identified three distinct epicardial subpopulations with specific gene expression profiles. The first subpopulation expressed tcf21, tbx18 and wt1b and appeared to represent the main epicardial layer. The second subpopulation expressed tbx18, but not tcf21 or wt1b. Instead, it expressed smooth muscle markers and seemed restricted to the bulbus arteriosus. The third epicardial subpopulation only expressed tcf21 and resided within the epicardial layer. I compared the single-cell subpopulations with transcriptomic bulk data and visualized the expression of marker genes to investigate their spatial distribution. Using ATAC sequencing, I additionally identified open regulatory regions located in proximity to subpopulation-specific marker genes and showed subpopulation-specific activity in vivo. My results detail distinct cell populations in the developing zebrafish epicardium, likely to fulfil distinct and specific cellular functions. Future experiments will involve targeting signature genes enriched within each epicardial subpopulation, such as those encoding Adrenomedullin a (first subpopulation), Alpha Smooth Muscle Actin (second subpopulation) and Claudin 11a (third subpopulation), employing cell type-specific genome editing to test whether and how the identified heterogeneity underlies distinct epicardial cell fates and functions. Taken together, my work adds significantly to the understanding of the cellular and molecular basis of epicardial development and can offer novel insights in the context of heart regeneration.
4
Harris, Michael Brennan. "Development of cardioprotection during an exercise program /." Digital version accessible at:, 1999. http://wwwlib.umi.com/cr/utexas/main.
Full text
5
Sharma, Pundrique Radheyshyam. "Programmed cell death during heart development." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272255.
Full text
6
Ranawake, Manoja, and n/a. "Development of the artificial heart for serial production." University of Canberra. Industrial Design, 1995. http://erl.canberra.edu.au./public/adt-AUC20061113.151545.
Full textAbstract:
Heart disease is the principal cause of death in most
industrialised countries. In the U.S.A. for example, 2.3 million individuals
suffer from chronic heart failure, with an annual increase in numbers of 17%.
It is estimated that 17,000 to 35,000 of them per year will die from this
disease if they are not given either a heart transplant or an artificial heart.
Unfortunately, the numbers of heart donors cannot meet the demand for
transplantation, and, at present, the artificial heart is a prohibitively
expensive alternative.
The total artificial heart (TAH) intended for the total replacement of the
natural heart is still some years away from realisation. However, the
ventricular assist device (VAD) which is used temporarily to maintain an ailing
heart is available now, although only in restricted numbers due to difficulties
in processing the biocompatible materials used during manufacture.
Consequently, such devices are expensive, costing anywhere from
AUS$30,000 for the pump head to AUS$200,000 for a complete system.
In this study, the Australian designed $quot;Spiral Vortex$quot; VAD was used to
investigate fabrication techniques for use in the eventual cost-effective
manufacture of a pump head costing approximately AUS$4,000. A second
VAD originally designed at the Kolff Laboratory, University of Utah, U.S.A.
was also used for comparative evaluation. The hard-shell Spiral Vortex VAD
is intended to be used outside the body, while the soft-shell Kolff VAD has the
advantage of being implantable for long-term use. They were cast from
epoxy resin and vacuum formed from polyurethane, respectively. Several
units of each were fabricated, including 60 of the Kolff VAD, for use in vitro
and in vivo experiments. From these experiments it was found that both the
Spiral Vortex and Kolff VADs could be fabricated to quality controllable
standards. The Kolff VAD was used exclusively in chronic animal
experiments, and was able to sustain sheep and goats for periods of up to
five weeks. Furthermore, it became evident that techniques used in
fabrication of the Kolff VAD could be adopted for use in the mass production
of the Spiral Vortex VAD.
The two other areas investigated in this study were the prosthetic heart
valves and drive systems used for an artificial heart. A high percentage of
the cost of an artificial heart is accounted for by the inflow/outflow valves.
The trileaflet valve used in the Kolff VAD, which mimics the natural heart
valve, was fabricated using inexpensive vacuum-forming techniques. Quality
control was found to be adequate, with good flow characteristics which could
be maintained for several weeks in animal experiments. Both the Spiral
Vortex and Kolff VADs are pulsation pumps which require a pneumatic driver
unit. This driver is the single most expensive component in a VAD system,
costing upwards of AUS$150,000. The theoretical efficiency of a compact
hydromechanical drive unit was investigated using a test rig to simulate an
original design based primarily on proprietary components. Results obtained
so far indicate that the proposed driver can operate only under limited
conditions as a result of its severe reduction in size.
By adopting mass production techniques wherever possible in the fabrication
of the VAD (pump head) and valves, and by reducing the cost and size of the
driver unit, it may therefore be possible to produce a cost effective ventricular
assist device system.
7
Sneesby, Kyra, and n/a. "Gene Expression in Embryonic Chick Heart Development." Griffith University. School of Biomolecular and Biomedical Science, 2003. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20030924.153514.
Full textAbstract:
Establishment of the biochemical and molecular nature of cardiac development is essential for us to understand the relationship between genetic and morphological aspects of heart formation. The molecular mechanisms that underly heart development are still not clearly defined. To address this issue we have used two approaches to identify genes involved in early chick cardiac development. Differential display previously conducted in our laboratory led to the identification of two gene fragments differentially expressed in the heart that are further described in this thesis. The full-length cDNA sequence of both eukaryotic translation initiation factor-2b (eIF-2b) and NADH cytochrome b5 reductase (b5R) were isolated using library screening. The upreglation of these genes during heart development is expected given the heart is the first functional organ to form in vertebrates and protein synthesis and cell metabolism at this stage of development is maximal. Limitations in the differential display approach led to the development and optimisation of a subtractive hybridisation approach for use with small amounts of cells or tissue. To focus on cardiac gene expression during the initial phases of heart development, subtractive hybridization was performed between the cardiogenic lateral plate mesoderm of Hamburger and Hamilton stage 4 embryos and the heart primordia of stage 9 embryos. Of the 87 independent clones identified by this procedure, 59 matched known sequences with high homology, 25 matched unknown expressed sequence tag (EST) sequences with high homology, and 3 did not match any known sequence on the database. Known genes isolated included those involved in transcription, translation, cell signalling, RNA processing, and energy production. Two of these genes, high mobility group phosphoprotein A2 (HMGA2) and C1-20C, an unknown gene, were chosen for further characterisation. The role of each gene in early chick heart development and indeed development in general, was addressed using techniques such as in situ hybridisation, transfection analysis, in ovo electroporation and RNAi. HMGA2 is a nuclear phosphoprotein commonly referred to as an architectural transcription factor due to its ability to modulate DNA conformation. In keeping with this function, HMGA2/GFP fusion protein was shown to localise to the nucleus and in particular, the nucleolus. In situ hybridisation analysis suggested a role for HMGA2 in heart and somite development. HMGA2 expression was first detected at HH stage 5 in the lateral plate mesoderm, a region synonymous with cells specified to the cardiac fate. HMGA2 was also strongly expressed in the presomitic segmental plate mesoderm and as somites developed from the segmental plate mesoderm, the expression of HMGA2 showed an increasingly more restricted domain corresponding to the level of maturation of the somite. Restriction of HMGA2 expression was first detected in the dorsal region of the epithelial somite, then the dorsomedial lip of the dermomyotome, and finally the migrating epaxial myotome cells. The novel intronless gene, C1-20C, predicts a protein of 148 amino acids containing a putative zinc finger binding domain and prenyl binding motif. Zinc binding assays showed that the zinc finger domain of C1-20C/MBP fusion protein bound over six times the quantity of zinc compared to MBP alone, although not in a 1:1 stoichiometric molar ratio. C1-20C/GFP fusion protein was shown to localise to as yet unidentified intracellular cytoplasmic vesicular compartments. These compartments did not colocalise with the endosome/lysosome pathway, aparently ruling out a role for C1-20C in protein trafficking, recycling or degradation. Expression of C1-20C in the chick embryo suggests a possible role in heart and notochord development and preliminary results using siRNA suggest that C1-20C is involved in normal heart looping.
8
Duong, Tiffany. "Mechanisms of NR2Fs in Heart Valve Development." University of Cincinnati / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505149242216719.
Full text
9
Makwana, Om. "THE EFFECTS OF TRICHLOROETHYLENE ON HEART DEVELOPMENT." Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/204310.
Full textAbstract:
Trichloroethylene (TCE; TRI; C2HCl3) is an organic solvent used as an industrial degreasing agent. Due to its widespread use and volatile nature, TCE is a common environmental contaminant. Trichloroethylene exposure has been implicated in the etiology of heart defects in human populations and animal models. Recent data suggest misregulation of Ca2+ homeostasis in a cardiomyocyte cell line after TCE exposure (Caldwell, Thorne et al. 2008). We hypothesized that misregulation of Ca2+ homeostasis alters myocyte function and leads to changes in embryonic blood flow. In turn, changes in cardiac flow are known to cause cardiac malformations. To investigate this hypothesis we dosed developing chick embryos in ovo with environmentally relevant doses of TCE (8 ppb and 800 ppb). We then isolated RNA from embryos at crucial time points in development for real-time PCR analysis of markers for altered blood flow. Based on this analysis, we observed effects on ET-1 (Endothelin-1), NOS-3 (Nitric Oxide Synthase-3) and Krüppel-Like Factor 2 (KLF2) expression relative to TCE exposure. Additionally, we assessed cardiomyocyte function by isolating chick E18 cardiomyocytes from embryos exposed to TCE in ovo. Cells were measured for rate of contraction after pulsing with extracellular Ca2+ and electrical stimulation at a frequency of 1.0 Hz. These functional data showed an effect on Ca2+ handling in cardiomyocytes exposed to TCE. To investigate an apparent non-monotypic effect in the heart where 8 ppb produced a stronger effect than 800 ppb, we isolated RNA from the developing heart and AV Canal to investigate the expression of several candidate Cytochrome P450s (CYPs) related to TCE metabolism. We observed a significant induction of multiple CYP2 family members in the developing heart after low dose TCE exposure. Together, these data suggest cardio-specificity of TCE as a teratogen and may reflect a requirement for normal calcium regulation of contractile function during organ development.
10
Sneesby, Kyra. "Gene Expression in Embryonic Chick Heart Development." Thesis, Griffith University, 2003. http://hdl.handle.net/10072/367647.
Full textAbstract:
Establishment of the biochemical and molecular nature of cardiac development is essential for us to understand the relationship between genetic and morphological aspects of heart formation. The molecular mechanisms that underly heart development are still not clearly defined. To address this issue we have used two approaches to identify genes involved in early chick cardiac development. Differential display previously conducted in our laboratory led to the identification of two gene fragments differentially expressed in the heart that are further described in this thesis. The full-length cDNA sequence of both eukaryotic translation initiation factor-2b (eIF-2b) and NADH cytochrome b5 reductase (b5R) were isolated using library screening. The upreglation of these genes during heart development is expected given the heart is the first functional organ to form in vertebrates and protein synthesis and cell metabolism at this stage of development is maximal. Limitations in the differential display approach led to the development and optimisation of a subtractive hybridisation approach for use with small amounts of cells or tissue. To focus on cardiac gene expression during the initial phases of heart development, subtractive hybridization was performed between the cardiogenic lateral plate mesoderm of Hamburger and Hamilton stage 4 embryos and the heart primordia of stage 9 embryos. Of the 87 independent clones identified by this procedure, 59 matched known sequences with high homology, 25 matched unknown expressed sequence tag (EST) sequences with high homology, and 3 did not match any known sequence on the database. Known genes isolated included those involved in transcription, translation, cell signalling, RNA processing, and energy production. Two of these genes, high mobility group phosphoprotein A2 (HMGA2) and C1-20C, an unknown gene, were chosen for further characterisation. The role of each gene in early chick heart development and indeed development in general, was addressed using techniques such as in situ hybridisation, transfection analysis, in ovo electroporation and RNAi.
HMGA2 is a nuclear phosphoprotein commonly referred to as an architectural transcription factor due to its ability to modulate DNA conformation. In keeping with this function, HMGA2/GFP fusion protein was shown to localise to the nucleus and in particular, the nucleolus. In situ hybridisation analysis suggested a role for HMGA2 in heart and somite development. HMGA2 expression was first detected at HH stage 5 in the lateral plate mesoderm, a region synonymous with cells specified to the cardiac fate. HMGA2 was also strongly expressed in the presomitic segmental plate mesoderm and as somites developed from the segmental plate mesoderm, the expression of HMGA2 showed an increasingly more restricted domain corresponding to the level of maturation of the somite. Restriction of HMGA2 expression was first detected in the dorsal region of the epithelial somite, then the dorsomedial lip of the dermomyotome, and finally the migrating epaxial myotome cells. The novel intronless gene, C1-20C, predicts a protein of 148 amino acids containing a putative zinc finger binding domain and prenyl binding motif. Zinc binding assays showed that the zinc finger domain of C1-20C/MBP fusion protein bound over six times the quantity of zinc compared to MBP alone, although not in a 1:1 stoichiometric molar ratio. C1-20C/GFP fusion protein was shown to localise to as yet unidentified intracellular cytoplasmic vesicular compartments. These compartments did not colocalise with the endosome/lysosome pathway, aparently ruling out a role for C1-20C in protein trafficking, recycling or degradation. Expression of C1-20C in the chick embryo suggests a possible role in heart and notochord development and preliminary results using siRNA suggest that C1-20C is involved in normal heart looping.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Biomedical Sciences
Full Text
11
Matos, Nieves Adrianna P. "Identification of novel genetic contributors for congenital heart disease by transcriptomic profiling of the developing embryonic mouse heart." The Ohio State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1618148539166683.
Full text
12
Courtney, Jennifer A. "The Role of Abnormal Placentation in Congenital Heart Defects." University of Cincinnati / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1623165569297281.
Full text
13
Tan, Sean. "Development of a dynamic model of a ventricular assist device for investigation of control systems." Ottawa, 1996.
Find full text
14
Kaarbo, Mari, and n/a. "The Role of RhoA in Early Heart Development." Griffith University. School of Biomolecular and Biomedical Science, 2005. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20060105.091005.
Full textAbstract:
RhoA is a small GTPase that acts as a molecular switch to control a variety of signal transduction pathways in eukaryotes. From an initial established role in the regulation of the actin cytoskeleton, RhoA has now been implicated in a range of functions that include gene transcription and regulation of cell morphology. In earlier studies from this laboratory that employed differential display and in situ hybridisation, RhoA was indicated as being up-regulated during the stages of early heart development in the developing chick embryo. Given the important effects of RhoA on both gene expression and morphology in other systems, it was hypothesised that RhoA plays a central role in the molecular mechanisms controlling cardiogenesis. This thesis describes investigations undertaken to elucidate the role of RhoA in these processes. As an initial approach to corroborate the earlier gene expression findings and provide further evidence for a role in tissue developmental mechanisms, RhoA proteins levels in the developing chick embryo were analysed using immunocytochemistry. These experiments demonstrated that RhoA is most abundant in heart-forming regions, findings compatible with the earlier gene expression studies and the proposed role of this protein in early heart development. Preliminary studies from this laboratory had also suggested that chick RhoA is expressed as different length mRNA transcripts that vary only in the 3' untranslated region (UTR). This thesis presents additional evidence for the existence of these different RhoA transcripts from experiments using Northern hybridisation and RT-PCR analyses. These analyses also serve to demonstrate that the second shortest RhoA transcript (designated RhoA2) is the most abundant transcript in developing heart tissue, in contrast to the situation in other embryonic tissues, findings that could be taken to suggest a possible role for this 3'UTR in developmental mechanisms that is yet to be elucidated. One potentially informative approach for testing the function of a protein in a biological system is to inhibit its expression and/or activity and observe the changes induced. The effects of inhibiting RhoA in early heart development and early organogenesis in the chick embryo model were investigated using small interfering RNAs (siRNA). Reduction in RhoA expression by siRNA treatment, as confirmed by real-time PCR, resulted in loss of heart tube fusion and abnormal head development, the former result providing further direct evidence of a role for RhoA in heart developmental processes. In order to investigate the function of RhoA specifically during the process of cardiomyocyte differentiation, an inducible model of cardiomyogenesis, P19CL6 cells, was used in combination with over-expression of different forms of mouse RhoA. The striking result from these investigations was that over-expression of the dominant negative mutant of mouse RhoA (mRhoAN19) prevented the differentiation of induced P19CL6 cells to the cardiomyocyte phenotype, results consistent with an essential role for RhoA in this cellular transition. The mechanism by which RhoA mediates its different cellular functions is unclear, however some studies have implicated RhoA in the regulation of transcription factors. To investigate such a mechanism as a possible explanation for the requirement of RhoA in cardiomyocyte differentiation, the P19CL6 inducible cell system over-expressing different forms of RhoA was analysed through real-time PCR to quantify the levels of transcription of genes known to play an important role in early heart development. These investigations indicated that RhoA inhibition causes an accumulation of the cardiac transcription factors SRF and GATA4 and the early cardiac marker cardiac-cx-actin. The expression of a protein is controlled by, among other factors, regulatory proteins that control transcription. To investigate factors in heart that potentially regulate RhoA expression at the molecular level, the chick RhoA gene organisation was analysed. The gene was shown to contain three introns that interrupt the protein coding sequence and at least one intron in the 5'UTR. Comparative RhoA gene studies indicated both an almost identical organisation and coding sequence of the chick, mouse and human RhoA genes, indicative of strict conservation of this gene during evolution. The putative promoter region of RhoA was predicted by computer analyses and tested for promoter activity using luciferase reporter analyses in non-differentiated and differentiated cardiomyocytes, using the inducible P19CL6 cell system. These investigations served to define a putative core promoter region that exhibited significantly higher promoter activity in differentiated cardiomyocytes than in non-differentiated cells, and other elements upstream of this core region that appear to be required for transcriptional regulation of RhoA. The majority of the consensus transcription factor sites identified in this putative promoter have been previously implicated in either heart development and/or organogenesis. These results therefore provide further, although indirect, evidence for an important role for RhoA in the molecular mechanisms controlling both cardiogenesis and embryogenesis in general. In summary, this thesis provides novel information on the role of RhoA in the processes of cardiogenesis and provides a firm foundation for continuing investigations aimed at elucidating the molecular basis of this contribution.
15
Bellomo, Daniela. "Development of heart asymmetry in the mammalian embryo." Thesis, St George's, University of London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243987.
Full text
16
Kaarbo, Mari. "The Role of RhoA in Early Heart Development." Thesis, Griffith University, 2005. http://hdl.handle.net/10072/366791.
Full textAbstract:
RhoA is a small GTPase that acts as a molecular switch to control a variety of signal transduction pathways in eukaryotes. From an initial established role in the regulation of the actin cytoskeleton, RhoA has now been implicated in a range of functions that include gene transcription and regulation of cell morphology. In earlier studies from this laboratory that employed differential display and in situ hybridisation, RhoA was indicated as being up-regulated during the stages of early heart development in the developing chick embryo. Given the important effects of RhoA on both gene expression and morphology in other systems, it was hypothesised that RhoA plays a central role in the molecular mechanisms controlling cardiogenesis. This thesis describes investigations undertaken to elucidate the role of RhoA in these processes. As an initial approach to corroborate the earlier gene expression findings and provide further evidence for a role in tissue developmental mechanisms, RhoA proteins levels in the developing chick embryo were analysed using immunocytochemistry. These experiments demonstrated that RhoA is most abundant in heart-forming regions, findings compatible with the earlier gene expression studies and the proposed role of this protein in early heart development. Preliminary studies from this laboratory had also suggested that chick RhoA is expressed as different length mRNA transcripts that vary only in the 3' untranslated region (UTR). This thesis presents additional evidence for the existence of these different RhoA transcripts from experiments using Northern hybridisation and RT-PCR analyses. These analyses also serve to demonstrate that the second shortest RhoA transcript (designated RhoA2) is the most abundant transcript in developing heart tissue, in contrast to the situation in other embryonic tissues, findings that could be taken to suggest a possible role for this 3'UTR in developmental mechanisms that is yet to be elucidated. One potentially informative approach for testing the function of a protein in a biological system is to inhibit its expression and/or activity and observe the changes induced. The effects of inhibiting RhoA in early heart development and early organogenesis in the chick embryo model were investigated using small interfering RNAs (siRNA). Reduction in RhoA expression by siRNA treatment, as confirmed by real-time PCR, resulted in loss of heart tube fusion and abnormal head development, the former result providing further direct evidence of a role for RhoA in heart developmental processes. In order to investigate the function of RhoA specifically during the process of cardiomyocyte differentiation, an inducible model of cardiomyogenesis, P19CL6 cells, was used in combination with over-expression of different forms of mouse RhoA. The striking result from these investigations was that over-expression of the dominant negative mutant of mouse RhoA (mRhoAN19) prevented the differentiation of induced P19CL6 cells to the cardiomyocyte phenotype, results consistent with an essential role for RhoA in this cellular transition. The mechanism by which RhoA mediates its different cellular functions is unclear, however some studies have implicated RhoA in the regulation of transcription factors. To investigate such a mechanism as a possible explanation for the requirement of RhoA in cardiomyocyte differentiation, the P19CL6 inducible cell system over-expressing different forms of RhoA was analysed through real-time PCR to quantify the levels of transcription of genes known to play an important role in early heart development. These investigations indicated that RhoA inhibition causes an accumulation of the cardiac transcription factors SRF and GATA4 and the early cardiac marker cardiac-cx-actin. The expression of a protein is controlled by, among other factors, regulatory proteins that control transcription. To investigate factors in heart that potentially regulate RhoA expression at the molecular level, the chick RhoA gene organisation was analysed. The gene was shown to contain three introns that interrupt the protein coding sequence and at least one intron in the 5'UTR. Comparative RhoA gene studies indicated both an almost identical organisation and coding sequence of the chick, mouse and human RhoA genes, indicative of strict conservation of this gene during evolution. The putative promoter region of RhoA was predicted by computer analyses and tested for promoter activity using luciferase reporter analyses in non-differentiated and differentiated cardiomyocytes, using the inducible P19CL6 cell system. These investigations served to define a putative core promoter region that exhibited significantly higher promoter activity in differentiated cardiomyocytes than in non-differentiated cells, and other elements upstream of this core region that appear to be required for transcriptional regulation of RhoA. The majority of the consensus transcription factor sites identified in this putative promoter have been previously implicated in either heart development and/or organogenesis. These results therefore provide further, although indirect, evidence for an important role for RhoA in the molecular mechanisms controlling both cardiogenesis and embryogenesis in general. In summary, this thesis provides novel information on the role of RhoA in the processes of cardiogenesis and provides a firm foundation for continuing investigations aimed at elucidating the molecular basis of this contribution.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Biomedical Sciences
Full Text
17
Darwich, Rami. "Identification of KLF13 Interacting Partners in the Heart." Thèse, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/20154.
Full textAbstract:
Identifying the molecular and genetic pathways important for heart development and deciphering the causes of CHD are still a challenging puzzle. A newly identified piece of this puzzle is KLF13, a member of the Krüppel-like family of zinc-finger proteins, was found to be important for atrial septation and ventricular trabeculation of Xenopus embryos. The protein is expressed predominantly in the heart, binds evolutionarily-conserved regulatory elements on cardiac promoters, and activates cardiac transcription.
In this study we examined KLF13 mechanism of action by investigating its transcriptional activity on the ANF promoter using a deletion/mutagenesis approach. We reported the identification of a new synergistic partnership between KLF13 and the individual cardiac transcription factors TBX5, NKX2.5, PEX1, and CATF1. Also, we localized KLF13’s transcriptional activation domain, the nuclear localization region/zinc-fingers, and the DNA binding zinc-fingers. This study will provide insight into the contribution of KLF13 to the development of CHDs.
18
Dohn, Tracy E. "Roles of Wnt signaling and Nr2f1a during zebrafish cardiac development." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1427983237.
Full text
19
Damen, Bas Stefaan, and bsdamen@hotmail com. "Design, Development, and Optimisation of a Culture Vessel System for Tissue Engineering Applications." Swinburne University of Technology. n/a, 2003. http://adt.lib.swin.edu.au./public/adt-VSWT20040512.125051.
Full textAbstract:
A Tissue Engineering (TE) approach to heart valve replacement has the aim of producing an implant that is identical to healthy tissue in morphology, function and immune recognition. The aim is to harvest tissue from a patient, establish cells in culture from this tissue and then use these cells to grow a new tissue in a desired shape for the implant. The scaffold material that supports the growth of cells into a desired shape may be composed of a biodegradable polymer that degrades over time, so that the final engineered implant is composed entirely of living tissue. The approach used at Swinburne University was to induce the desired mechanical and functional properties of tissue and is to be developed in an environment subjected to flow stresses that mimicked the haemodynamic forces that natural tissue experiences. The full attainment of natural biomechanical and morphological properties of a TE structure has not as yet been demonstrated.
In this thesis a review of Tissue Engineering of Heart Valves (TEHVs) is presented followed by an assessment of biocompatible materials currently used for TEHVs. The thrust of the work was the design and development of a Bioreactor (BR) system, capable of simulating the corresponding haemodynamic forces in vitro so that long-term cultivation of TEHVs and/or other structures can be mimicked. A full description of the developed BR and the verification of its functionality under various physiological conditions using Laser Doppler Anemometry (LDA) are given. An analysis of the fluid flow and shear stress forces in and around a heart valve scaffold is also provided.
Finally, preliminary results related to a fabricated aortic TEHV-scaffold and the developed cell culture systems are presented and discussed. Attempts to establish viable cell lines from ovine cardiac tissue are also reported.
20
Darwich, Rami. "Functional Analysis of KLF13 in the Heart." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/34317.
Full textAbstract:
Congenital heart defects (CHD) are the largest class of birth defects in humans and are a major cause of infant mortality and morbidity. Deciphering the molecular and genetic etiologies central for heart development and the pathogenesis of congenital heart diseases (CHD) is a challenging puzzle. We have previously demonstrated that the zinc-finger kruppel-like transcription factor KLF13, expressed predominantly in the atria, binds evolutionarily conserved regulatory elements known as CACC-boxes and transcriptionally activates several cardiac promoters. KLF13 loss of function in Xenopus embryos was associated with cardiac developmental defects underscoring its critical role in the heart. In the current study, using in vivo and in vitro approaches, we examined KLF13’s mechanisms of action and its interaction with other cardiac regulators. To test the evolutionary conserved role in the mammalian heart, we deleted the Klf13 gene in transgenic mice using homologous recombination. Mice with homozygote deletion of Klf13 were born at reduced frequency owing to severe heart defects. We also report the existence of a novel isoform of KLF13, referred to here as KLF13b. Furthermore, we report that KLF13 interacts biochemically and genetically with the T-box transcription factor TBX5 which is a key regulator of heart development. Our data provide novel insight into the role of KLF13 in cardiac transcription and suggest that KLF13 maybe a genetic modifier of congenital heart disease. Furthering our knowledge of protein-protein interactions and gene transcription will enhance genotype-phenotype correlation and contribute to better understanding of the etiology of CHD.
21
Song, Yuntao. "Epigenetic repression of retinoic acid responsive genes for cardiac outflow tract formation." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1563295948947138.
Full text
22
Nagy, I. I. (Irina I. ). "Wnt-11 signaling roles during heart and kidney development." Doctoral thesis, Oulun yliopisto, 2014. http://urn.fi/urn:isbn:9789526204666.
Full textAbstract:
Abstract Organogenesis involves precursor cells proliferation, differentiation along with their coordinated organization into precise multicellular arrangements by planar cell polarity (PCP) pathways. The beta-catenin independent/non-canonical type of Wnt-11 signaling has been known as a PCP modulator during development. In this thesis were analyzed the roles of Wnt-11 in heart and kidney development by using in vivo functional genomics technologies. We show that the Wnt-11 gene is important for murine ventricular myocardium development, since Wnt-11 deficiency in early cardiogenesis leads to impaired organization and maturation of mouse ventricular cardiomyocytes, causing primary cardiomyopathy with in utero lethality. Wnt-11 coordinates the co-localized expression of the cell adhesion molecules N-cadherin and β-catenin, which are critical for the spatially specific organization of cardiomyocytes. We show that Wnt-11 deficiency causes primary hypertrophic and noncompaction cardiomyopathy in adult mice, with consequences for regional myocardium function. The Wnt family of secreted signals has been implicated in kidney tubule development and tubular cystic diseases such as polycystic kidney disease. We show here that Wnt-11 is expressed in mature nephrons and is involved in late steps of nephrogenesis, since the kidney tubule organization is deregulated in Wnt-11 deficient kidneys, to enlarged lumen with increased convolution. These tubule abnormalities are associated with glomerular microcyst formation and kidney failure. Wnt-11 deficiency reduced significantly Wnt-9b expression, a critical signal for PCP-mediated kidney tubule elongation. In the cortical region this associated with reduced expression of nephron and stromal progenitor cell marker. The results in this thesis point out that Wnt-11 function is required for proper myocardium organization and maturation as well as proper morphogenesis of the kidney tubules during the embryonic and postnatal developmental stages. Wnt-11 knockout phenotypes depend on the genetic background, similarly to human congenital disease. This data may be relevant for human congenital cardiomyopathy and glomerulocystic kidney disease studiesTiivistelmä Alkion sisäelinten kehityksen aikana esisolut lisääntyvät ja erilaistuvat muodostaen tarkoin määriteltyjä monisoluisia rakenteita. Muodostuvan kudosrakenteen määrittelyssä erilaiset solusignaalit ovat keskeisessä asemassa. Yksi näistä on nk. Wnt signaali perhe. Wnt perheeen jäsen Wnt-11 tehtävät on huonosti tunnettu. Wnt-11 viestittää ilmeisesti nk. planaaristen solupolariteettireittien (PCP) avulla, joka on beeta-kateniinista riippumattoman nk. ei-kanonisen Wnt signaali. Väitöskirjatyössä selvitettiin Wnt-11:n vaikutuksia sydämen ja munuaisten kehitykseen in vivo funktionaalisten genomisten menetelmien avulla. Ihmisen synnynnäiset kardiomyopatiat ovat sydänlihaksen ensisijaisia vaurioita, joiden taustalla on sydänlihaksen kehityshäiriö. Tutkimuksessa osoitetaan, että Wnt-11-geenillä on tärkeä merkitys hiiren sydänkammion kehitykselle, koska Wnt-11-geenin puute sydämen varhaisen kehityksen vaiheessa johtaa sydänlihassolujen järjestäytymisen ja kypsymisen häiriintymiseen, jolloin seurauksena on ensisijaisesta kardiomyopatiasta johtuva sikiökuolema. Wnt-11 koordinoi kahden solukiinnitysmolekyylin, N-kadheriinin ja β-kateniinin, samanaikasta ilmentymistä. Kyseiset molekyylit ovat keskeisen tärkeitä sydänlihasssolujen spatiaalisen järjestäytymisen kannalta. Tutkimuksessa osoitetaan, että Wnt-11-puutos aiheuttaa aikuisilla hiirillä ensisijaista sydänlihaksen liikakasvua ja trabekuloivaa kardiomyopatiaa, mikä vaikuttaa sydänlihaksen toimintaan. Tuloksilla voi olla merkitystä tutkittaessa ihmisen synnynnäisiä kardiomyopatioita. Wnt-signaaliperheen on osoitettu olevan yhteydessä munuaisputken kehitykseen ja sen sairauksiin, kuten munuaisten monirakkulatautiin. Väitöstutkimuksessa osoitetaan, että Wnt-11 ilmentyy kypsissä nefroneissa ja että se osallistuu nefrogeneesiin myöhempiin vaiheisiin, koska munuaisputken kehityksen säätely on poikkeavaa niissä munuaisissa, joista Wnt-11 puuttuu. Seurauksena on laajentunut, normaalia poimuttuneempi luumen. Munuaisputken poikkeavuuksilla oli yhteyttä munuaiskerästen mikrokystien muodostumiseen sekä munuaisten vajaatoimintaan. Wnt-11 -puute vähensi huomattavasti Wnt-9b-ilmentymistä, joka on PCP-välitteisen munuaisputken pidentymisen kannalta keskeisen tärkeä signaali. Kortikaalialueella Wnt9b:n vaimennussäätely liittyi poikkeavaan solujen lisääntymiseen, apoptoosiin ja kypsymiseen sekä vähentyneeseen nefroni- ja stroomakantasolujen merkkiaineen ilmentymiseen. Väitöskirjatutkimuksen tulokset viittaavat siihen, että Wnt-11 -toiminto on välttämätön sydänlihaksen normaalin muodostumisen ja kypsymisen sekä munuaisputken normaalin morfogeneesin kannalta sikiövaiheen ja syntymän jälkeisen kehityksen aikana. Wnt-11 -poistogeenisen hiiren fenotyypi riippuu geneettisestä tausta, samaan tapaan kuin ihmisen synnynnäisissä sairauksissa. Väitöstutkimuksesta saatavalla tiedolla voi olla merkitystä tutkittaessa ihmisen synnynnnäistä kardiomyopatiaa ja munuaisten monirakkulatautia
23
Zhang, Bo. "The Role of Claudin-5 on Xenopus Heart Development." NCSU, 2008. http://www.lib.ncsu.edu/theses/available/etd-12172008-131757/.
Full textAbstract:
Claudin-5 is an important member of the claudin gene family. The expression of claudin-5 in the heart of Xenopus laevis was determined by whole mount in situ hybridization. RNA over expression and knock down experiments demonstrated that claudin-5 is critical for heart development. Meanwhile, claudin-5 down regulated bone morphogenetic protein 4 (BMP4) expression in early stage through upregulating chordin (chd). In addition, other pathways such as estrogen hormone and transforming growth factor-β (TGF-β) may also affect claudin-5 activity. The results show that claudin-5 plays an important role in heart development and is involved in a complex pathway of gene regulation. The mRNA expression of claudin-12, another member of claudin protein family was also determined from cleavage stage to tadpole stage by whole mount in situ hybridization.
24
Cagenello, Scott Anthony. "Plugged into the heart : service-learning and student development /." Access Digital Full Text version, 1993. http://pocketknowledge.tc.columbia.edu/home.php/bybib/11534060.
Full textAbstract:
Thesis (Ed.D.)--Teachers College, Columbia University, 1993.Includes tables. Typescript; issued also on microfilm. Sponsor: L. Lee Knefelkamp. Dissertation Committee: Dawn R. Person. Includes bibliographical references (leaves 269-274).
25
Vrljičak, Pavle Josip. "Genomic analysis of embryonic heart development in the mouse." Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/28814.
Full textAbstract:
Malformations of the cardiovascular system are the most common type of birth defect in humans, affecting predominantly the formation of valves and septa. While many studies have addressed the role of specific genes during valve and septa formation, a global understanding is still largely incomplete. To address this deficit we have undertaken a genome-wide transcriptional profiling of the developing heart in the mouse. We generated and analyzed 19 Serial Analysis of Gene Expression (SAGE) libraries representing different regions of the mouse heart at multiple stages of embryonic development.
We speculated that genes important for heart valve development would be differentially expressed in the valve forming regions, and have dynamic temporal expression patterns. We used our dataset to identify a novel list of valve enriched genes. Using k-means cluster analysis we also uncovered 14 distinct temporal gene expression patterns in the developing valves. Unique temporal expression patterns were found to be enriched for specific signalling pathway members and functional categories such as signal transduction, transcription factor activity, proliferation and apoptosis.
The most highly expressed transcription factor within the developing valves was found to be Twist1. Analysis of gene expression changes in the Twist1 null developing valves revealed a novel phenotype consistent with a role of TWIST1 in controlling differentiation of mesenchymal cells following their transformation from endothelium in the mouse. Our data suggests that TWIST1 directly activates valve specific and cell motility gene expression in the atrio-ventricular canal, while suppressing expression of valve maturation markers.
This work provides the first comprehensive temporal and spatial gene expression dataset for heart development during formation of the heart valves. It is a valuable resource for the elucidation of the molecular mechanisms underlying heart development.
26
Gray, Warren Dale. "Development of therapeutic systems to treat the infarcted heart." Diss., Georgia Institute of Technology, 2014. http://hdl.handle.net/1853/53429.
Full textAbstract:
Cardiovascular disease is the leading cause of morbidity and mortality in developed nations, and heart disease is predicted to remain the leading killer for the foreseeable future. Acute myocardial infarctions—nearly 1.1 million annually occurring in the U.S. alone—are the major cardiovascular disease subgroup. Current treatments for myocardial infarction are limited to interventions that serve to mitigate the initial insult, but clinical applications to protect or regenerate damaged myocardium are lacking. This dissertation examines three therapeutic systems to treat the infarcted heart. First, the decoration of a polymeric nanoparticle with N-acetylglucosamine for the uptake of anti-apoptotic therapeutics to ameliorate cardiomyocyte cell death. Second, novel dendrimeric structure architecture to allow for regioselected decoration of ligands to induce angiogenesis. Third, exosomes secreted from hypoxic cardiac progenitor cells as a naturally derived therapeuticfor angiogenesis and anti-fibrosis, and to provide bio-inspired clues for future therapies.
27
Ali, Mohd Alauddin Mohd. "Development of a portable fetal and maternal heart recorder." Thesis, University of Nottingham, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239928.
Full text
28
Leong, Fong Tat Eugene. "Hop : an unusual homeobox gene involved in heart development." Thesis, University of Leeds, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.438484.
Full text
29
Singer, C. "The development of prototype prosthetic synthetic fibre heart valves." Thesis, University of Leeds, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.235412.
Full text
30
Fair, Merlin John Casper. "Development of whole-heart myocardial perfusion magnetic resonance imaging." Thesis, Imperial College London, 2017. http://hdl.handle.net/10044/1/55941.
Full textAbstract:
Myocardial perfusion imaging is of huge importance for the detection of coronary artery disease (CAD), one of the leading causes of morbidity and mortality worldwide, as it can provide non-invasive detection at the early stages of the disease. Magnetic resonance imaging (MRI) can assess myocardial perfusion by capturing the rst-pass perfusion (FPP) of a gadolinium-based contrast agent (GBCA), which is now a well-established technique and compares well with other modalities. However, current MRI methods are restricted by their limited coverage of the left ventricle. Interest has therefore grown in 3D volumetric \whole-heart" FPP by MRI, although many challenges currently limit this. For this thesis, myocardial perfusion assessment in general, and 3D whole-heart FPP in particular, were reviewed in depth, alongside MRI techniques important for achieving 3D FPP. From this, a 3D 'stack-of-stars' (SOS) FPP sequence was developed with the aim of addressing some current limitations. These included the breath-hold requirement during GBCA rst-pass, long 3D shot durations corrupted by cardiac motion, and a propensity for artefacts in FPP. Parallel imaging and compressed sensing were investigated for accelerating whole-heart FPP, with modi cations presented to potentially improve robustness to free-breathing. Novel sequences were developed that were capable of individually improving some current sequence limits, including spatial resolution and signal-to-noise ratio, although with some sacri ces. A nal 3D SOS FPP technique was developed and tested at stress during free-breathing examinations of CAD patients and healthy volunteers. This enabled the rst known detection of an inducible perfusion defect with a free-breathing, compressed sensing, 3D FPP sequence; however, further investigation into the diagnostic performance is required. Simulations were performed to analyse potential artefacts in 3D FPP, as well as to examine ways towards further optimisation of 3D SOS FPP. The nal chapter discusses some limitations of the work and proposes opportunities for further investigation.
31
Hiltunen, Jukka. "Neurotropic factors in rodent heart : from development to pathophysiology." Helsinki : University of Helsinki, 2001. http://ethesis.helsinki.fi/julkaisut/eri/biote/vk/hiltunen/.
Full text
32
Sparks, Kenton L. "Jeremiah's development of Deuteronomy's anthropological term LB/LBB." Theological Research Exchange Network (TREN), 1990. http://www.tren.com.
Full text
33
Ching, Yung-Hao. "Molecular genetics of human atrial septal defects." Thesis, University of Nottingham, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246413.
Full text
34
Glenn, Nicole O. "Roles of alpha-cardiac actin during zebrafish heart development and the role of etsrp/etv2during zebrafish primitive neutropoiesis." University of Cincinnati / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1368013063.
Full text
35
Whitcomb, Elizabeth Jamieson. "Identification of GATA4 Regulatory Mechanisms of Heart Development and Disease." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/38830.
Full textAbstract:
The development and function of the heart is governed by a conserved set of transcription factors (TFs) that regulate gene expression in a cell-type, time point and stimulus driven manner. Of these core cardiac TFs, the most ubiquitously expressed is the zinc finger protein GATA4. In cardiomyocytes, GATA4 is central to proliferation, differentiation, hypertrophy and induction of pro-survival pathways. In cardiac endothelial cells, it is required for valve and septal development, although the exact mechanisms remain unclear. To regulate such a wide array of functions in a spatially and temporally controlled manner, GATA4 interacts with specific protein partners, the majority of whom have been identified in cardiomyocytes. However, a complete understanding of the protein interactome of GATA4, particularly in cardiac endothelial cells, has not yet been achieved. Using a mass spectrometry-based approach, we have identified a series of novel GATA4 interacting partners in cardiac endothelial cells. 3xFlag GATA4 was stably overexpressed via retroviral transduction in the TC13 cardiac endothelial precursor cell line, immunoprecipitated from nuclear protein extracts and sent for HPLC-ESI-MS/MS. Several novel GATA4 interacting partners were identified including the chaperone protein Heat Shock Protein 70 (HSP70), the inducible orphan nuclear receptor Nerve Growth Factor 1β (NGFIβ, NUR77) and the Drosophila-Binding/Human Splicing protein family members Non-POU Domain Containing Octamer Binding Protein (NONO) and Paraspeckle 1 (PSPC1). Chapter 1 discusses the interaction between GATA4 and HSP70 and its role in cardiomyocyte survival upon exposure to chemotherapeutic agent Doxorubicin (DOX). HSP70 binds directly to GATA4, preventing DOX-mediated cleavage and degradation by Caspase-1, cardiomyocyte cell death and heart failure. Chapter 2 focuses on the cooperative interaction between GATA4 and NUR77 in cardiac microvascular endothelial cells and its central role in myocardial angiogenesis in response to pressure overload. The GATA4-NUR77 complex transactivates the promoter of Angiopoietin-Like 7 (ANGPTL7), a secreted pro-angiogenic chemotactic factor, triggering endothelial cell proliferation and tube formation in cultured cardiac endothelial cells and increasing myocardial capillary density in vivo. Chapter 3 discusses the interaction between GATA4 and the DBHS proteins NONO and PSPC1 in the regulation of cardiac development. These proteins play opposing roles when bound to GATA4 as PSPC1 enhances GATA4 activation of critical cardiac promoter targets and NONO acts as a rheostat to repress GATA4 activity. In vivo, loss of NONO results in left ventricular non-compaction consistent with humans with loss-of-function mutations. However, simultaneous Gata4 haploinsufficiency partially rescues this phenotype. Together, this data identifies multiple novel cell type and time point specific GATA4 protein partners and sheds light on GATA4 regulatory mechanisms in cardiac development and disease.
36
Peacock, Jacqueline D. "The Role of Sox9 in Heart Valve Development and Disease." Scholarly Repository, 2011. http://scholarlyrepository.miami.edu/oa_dissertations/543.
Full textAbstract:
Heart valve structures open and close during the cardiac cycle to provide unidirectional blood flow through the heart, critical for efficient cardiovascular function. Valve dysfunction results in either incomplete opening or incomplete closure of the valve. Both types of valve dysfunction decrease efficiency of blood flow, increasing the load on the myocardium and leading to secondary heart disease such as pathological hypertrophy and heart failure. There are currently no effective treatments to prevent or slow the progression of valve disease, and there are no pharmacological treatments for advanced valve disease. Although most valve disease is associated with aging, increasing evidence suggests that valve disease often has origins in development. Congenital valvuloseptal defects affect many newborns, ranging from life-threatening malformations requiring immediate repair to more subtle, often undiagnosed defects that increase susceptibility to valve disease later in life. Therefore, an improved understanding of the mechanisms of heart valve formation and maintenance of adult valves may serve as an important step in improving valve disease treatment options. In this work, the mechanisms of normal valve development and the role of Sox9 in developing and mature valves are further studied. The temporal and spatial expression of extracellular matrix genes and proteins are examined throughout normal murine valve development. Sox9 function in the processes of valve development and valve maintenance is examined using mouse models of conditional Sox9 loss-of-function. Heart valve phenotypes in mice with reduced Sox9 function are examined throughout development and in adult mice with resultant calcific valve disease. The possible causative mechanisms of calcific valve disease in mice with reduced Sox9 function are further investigated by identification of novel possible targets of Sox9 transcriptional regulation. Together these studies improve our understanding of heart valve development, characterize a model of heart valve calcification with genetic etiology, and identify and characterize novel targets of Sox9.
37
Smith, Steven C. "Control of heart development in the Mexican axolotl (Ambystoma mexicanum)." Thesis, University of Ottawa (Canada), 1990. http://hdl.handle.net/10393/5940.
Full textAbstract:
The locations and migration of the embryonic primordia which form the heart are well known. However, the processes whereby the heart-forming mesoderm is induced, and the later mechanisms controlling the differentiation and morphogenesis of the heart are only poorly understood for any system. An important model system for studying heart induction and differentiation is the cardiac-lethal (c) mutant in the axolotl (Ambystoma mexicanum). Embryos homozygous for the c gene develop hearts which never begin to beat, become severely deformed due to the lack of circulation, and die shortly after hatching. The mutation was believed to affect the tissue responsible for heart induction, the anterior (pharyngeal) endoderm, rendering it incapable of supplying the appropriate inductive stimuli. The inductive failure hypothesis is largely based on an assumption. The assumption is that the timing of heart induction is the same in the axolotl as has been reported for another urodele species (Taricha torosa). As well, this hypothesis is based on the finding that wild-type heart mesoderm does not form beating hearts when transplanted into c/c embryos at late tailbud stages 28-29. On the basis of this evidence, it has been suggested that wild-type heart mesoderm does not receive the proper inductive signals in the mutant environment. However, it has also been suggested that the induction occurs much earlier in another species of Ambystoma than in T. torosa; the timing of the inductive process in the axolotl has never been determined. The presence of a specific activator and inhibitor of heart differentiation, both produced by the heart mesoderm itself, provides evidence that the later phases of heart formation (i.e. the organization of contractile proteins into functional sarcomeres, and possibly the early morphogenesis of the heart tube) are probably under the control of a two-morphogen reaction-diffusion system. Such systems have been demonstrated to control pattern formation in one invertebrate organism, and have been proposed to control morphogenesis in a variety of other systems. However, this study is the first direct, experimental evidence for a reaction-diffusion mechanism controlling the development of any vertebrate organ system. (Abstract shortened by UMI.)
38
Dunn, Jeremy. "Genetic influences on the premature development of coronary heart disease." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/mq24837.pdf.
Full text
39
Kim, Sung Ouk. "Regulation of protein kinases during postnatal development of rat heart." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ34562.pdf.
Full text
40
Seemann, Gunnar. "Modeling of electrophysiology and tension development in the human heart." Karlsruhe : Univ.-Verl, 2005. http://deposit.d-nb.de/cgi-bin/dokserv?idn=976559668.
Full text
41
Burton, Rebecca-Ann Beatrice. "Development of individualised whole heart models with para-cellular resolution." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.526547.
Full text
42
Ferentzi, Hannah Christine [Verfasser]. "Development of Children with Congenital Heart Disease / Hannah Christine Ferentzi." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2019. http://d-nb.info/1202042694/34.
Full text
43
Osuala, Kingsley. "Genetic and physiological contribution of adrenergic cells in heart development." Doctoral diss., University of Central Florida, 2011. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/4999.
Full textAbstract:
Bcmo-1 is a well known retinoic acid responsive gene, suggesting that the loss of adrenergic hormones in the Dbh-/- mouse heart may result in a deregulation of retinoic acid synthesis and further an alteration in the concentration of retinoic acid present in the embryonic tissue of adrenergic hormone deficient embryos. In addition, we utilized a genetic mouse model that expresses greek lower case letter beta]-galactosidase (greek lower case letter beta])-Gal) in cells capable of synthesizing epinephrine in order to identify the spatial and temporal distribution of adrenergic-derived cells in the developing heart. The model was designed so that cells capable of expressing the gene phenylethanolamine N-methyltransferase (Pnmt), which is responsible for the synthesis of epinephrine, also produce the enzyme greek lower case letter beta])-Gal as a reporter. The resulting presence of the greek lower case letter beta]-Gal enzyme can be visualized using greek lower case letter beta]-Gal substrate called XGAL, which is converted into a blue precipitate when cleaved by the greek lower case letter beta]-Gal enzyme. Evaluation of the location of these cells in the embryonic heart showed a preferential distribution at the atrioventricular sulcus at E10.5, and later at E18.5 a more widely distributed ventricular pattern was observed. In addition, the right atrium showed a cluster of XGAL positive cells (blue cells) near the region of the sinoatrial node, while the distribution of XGAL positive cells in the left atrium was quite diffuse. Interestingly, when the adult heart was examined, it was discovered that cells capable of synthesizing epinephrine (adrenergic-derived) are found predominately on the left side of the heart. This left-sided distribution appears to be non-random and non-uniform, since specific regions are consistently XGAL positive, but not every cell in each region.; The adrenergic hormones norepinephrine (NE) and epinephrine (EPI) are essential for cardiovascular development as embryos lacking NE/EPI begin to die abruptly between embryonic days 10.5 and 11.5 due to apparent cardiac failure. The objective of this research aims to elucidate the mechanism of the embryonic fatality observed in the NE/EPI deficient mouse model. Here we utilized the dopamine greek lower case letter beta]-hydroxylase knockout (Dbh-/-) mouse model, which lacks the gene and subsequent enzyme necessary for the conversion of dopamine to norepinephrine. Embryonic mouse hearts were extracted from Dbh+/+ (control) and Dbh-/- (experimental model) mice for mRNA transcript expression profiling. These studies were performed using the Affymetrix Mouse Genome 430A 2.0 Arrays and quantitative real-time RT-PCR. Gene expression data suggests a novel connection between the ability of the heart to synthesize adrenergic hormones and the gene expression of enzymes involved in the synthesis of retinoic acid. Specifically, we found a statistically significant change in transcriptional expression of the retinol binding protein-1 (Rbp-1), retinol dehydrogenase 12 (Rdh-12) and the beta carotene monooxygenase-1(Bcmo1) genes in the E10.5 Dbh-/- mouse heart. The gene expression of Rbp-1 and Rdh-12 were increased 1.4 fold and 2.1 fold on the microarray, respectively. The proteins translated from these genes play central roles in the transport and enzymatic conversion of precursor molecules in the pathway of retinoic acid biosynthesis. Additionally, we found that the expression of Bcmo-1, an enzyme responsible for the breakdown of beta carotene to the retinoic acid precursor retinal, was down regulated 2.7 fold in the Dbh-/- heart based on microarray assessment.; Whole mount and 3-dimensional reconstruction of the greek lower case letter beta]-Gal staining showed that these cells traverse the depth of the heart at the mid-ventricular and apical regions. This finding is quite interesting and may provide new knowledge about the functional and structural characteristics of the adult heart. One observation is that these cells may contribute to the cardiomyopathy known as Tako-Tsubo or "Broken Heart" syndrome. The syndrome is characterized by left ventricular dysfunction during bouts of stress. Also, of particular intrigue is the anatomical correlation of the adrenergic derived cells and the helical ventricular myocardial band (HVMB). Careful examination of the spatial and directional pattern of these cells within the myocardium suggests they contribute primarily to a specific section of the HVMB. The significance of this finding is yet to be uncovered. Taken collectively, this study has shown a novel connection between two crucial developmental signaling pathways. Adrenergic hormone and retinoic acid signaling can now be viewed as cooperative partners in the development of the embryonic heart. In addition, this study has also shown that adrenergic derived cells in the adult heart have a distinctive left-sided distribution, which is non-random, non-uniform, and shows interesting features suggesting an anatomical connection to the HVMB and a clinical association to Tako-Tsubo syndrome. These findings will appreciably contribute to the knowledge base of the scientific community.ID: 030423430; System requirements: World Wide Web browser and PDF reader.; Mode of access: World Wide Web.; Thesis (Ph.D.)--University of Central Florida, 2011.; Includes bibliographical references (p. 69-76).
Ph.D.
Doctorate
Burnett School of Biomedical Sciences
Graduate Studies
Biomedical Sciences
44
Cooper, Brian. "Regulation of two muscle-specific genes during Xenopus heart development." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327029.
Full text
45
Rozeik, Monica Mary. "Development of a reinforced synthetic heart valve for precutaneous delivery." Thesis, University of Strathclyde, 2013. http://digitool.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=25550.
Full textAbstract:
Approximately 30% of patients with aortic stenosis over the age of 75 years are refused surgery on the grounds of technical or high risk complications. Following the onset of symptoms, prognosis is very poor if left untreated. Transcatheter aortic valves intervention (TAVI) has paved the way for valve replacement in high risk patients without the need for open heart surgery. The current market approved valves can be delivered percutaneously through the femoral artery or transapically to the beating heart, deployed over the calcified leaflets and begin functioning immediately. Complications with the current TAVI valves include a requirement for a large delivery sheath which leads to major vascular bleeding. Additionally, these valves use pericardial leaflets, which are too thick to collapse into a small catheter and have a propensity to calcify. It is therefore the objective of this thesis to develop an ultra-thin reinforced synthetic leaflet to reduce the delivery profile and facilitate deployment though a peripheral artery. Polyurethane films reinforced with multi-walled carbon nanotubes were solvent cast and tested for changes to the mechanical properties. Dip coated composite valves with varying content of carbon nanotubes were then developed and tested in a high cycle durability tester. The stiffness of composites was found to improve overall with increasing nanotube content. However, fatigue life was found to be compromised, with only the 0.125% MWNT-TPU composite material having similar fatigue life to the neat TPU. The durability of the leaflets was also severely compromised when the thickness was dropped below 50 μm. Leaflet stresses were also reportedly highest at the commissures and the belly region. A valve having sufficiently thin leaflets (130 μm) was developed from a harder grade of polyurethane and has survived 23 million cycles to date. It is believed that a thin and durable leaflet can be achieved using harder grades of polyurethanes reinforced with low carbon nanotube concentrations.
46
Pall, Gurman Singh. "Characterisation of gene-trap integrations expressed during mouse heart development." Thesis, University of Edinburgh, 1998. http://hdl.handle.net/1842/15575.
Full textAbstract:
A gene-trap strategy in embryonic stem (ES)cells has been employed to identify and characterise genes involved in heart development. This work describes the characterisation of two gene-trap integrations (R68 and R124), including identification of endogenous trapped gene sequences and analysis to determine the function of the trapped genes. Molecular analysis of the R68 and R124 gene-trap integrations has shown the use of cryptic splice sites within the gene-trap vector indicating the vector has integrated into an exon in both gene-trap cell lines. The unpredicted integration of a gene-trap vector into an exon still results in the expression of the reporter gene. Sequence data indicates a novel gene has been trapped by the R124 gene-trap integration. The structure of the R124 integration in the genome has been predicted based upon sequencing data and restriction fragment length polymorphism analysis. The R124 gene-trap integration has been mapped to chromosome 5 in the mouse genome. Beating cardiomyoctyes generated from the in vitro differentiation of R68 and R124 ES cells express the reporter gene. Embryos heterozygous for the R124 gene-trap integration express reporter gene activity in the developing heart throughout gestation. In the adult the reporter gene is expressed in the heart, kidney, testis, ovary and brain. Function of the trapped gene was assessed by generating animals homozygous for the R124 integration. 60% of animals homozygous for the integration die shortly after birth. This lethality is associated with a right ventricle heart defect. Surviving homozygote males show enlarged hearts and kidneys. The surviving homozygote males are also infertile, histological analysis has shown no mature sperm in the testes of homozygote males.
47
Prickett, Adam. "The epigenetics and role of Dopa Decarboxylase in heart development." Thesis, King's College London (University of London), 2013. https://kclpure.kcl.ac.uk/portal/en/theses/the-epigenetics-and-role-of-dopa-decarboxylase-in-heart-development(fc53be8d-af43-4fac-9160-626ee8bf4f04).html.
Full textAbstract:
Genomic imprinting in mammals subjects a handful of genes to silencing on one allele depending on the parent-of-origin of that allele. The Ddc_exonla gene transcript is under the control of genomic imprinting in the developing and neonatal mouse heart with transcription occurring solely on the paternally inherited allele, with the maternally inherited allele epigenetically silenced. In all other tissues where Ddc_exonla is expressed transcription occurs from both parentally inherited alleles. CTCF plays a central role in controlling gene expression by regulating chromatin organisation, and has been shown to be fundamental for imprinting of the Igf2/H19 locus through its binding to the germline differentially methylated region (gDMR). This thesis explores the occurrence of CTCF binding both genome-wide and at imprinting gDMRs in mouse brain in order to assess its relevance to the control of transcription in vivo. 49,358 significant binding sites are detected across the genome and binding is enriched at gene coding regions but depleted at distal intergenic regions. 12/20 (60%) imprinted gDMRs are bound by CTCF, of these five bind in a parent-of-origin specific manner implicating CTCF in the control of a subset of imprinted genes including Ddc_exonla. Comparative analysis of CTCF binding in multiple tissues shows a high degree of overlap, and Motif analysis reveals CTCF binds the same canonical motif sequence in each tissue. CTCF binding in the absence of the canonical motif is more tissue-specific. Ddc_exonla expression is imprinted in the developing heart but is bi-allelic in brain, and the mechanism of imprinting is not known. To explore a model for imprinting control the epigenetic profile of the Ode imprinted locus was examined in detail. Methylation analysis reveals several regions that are differentially methylated between heart and brain. One region constitutes a CpG rich region at the promoter of GrblO, another imprinted gene located adjacent to Ddc_exonla. The second region is at the promoter of AK0066690, a non-coding antisense transcript which initiates in intron four of Ddc_exonla. CTCF binding at the Ddc/GrblO locus is assayed in heart and brain, and binding is invariant between tissue types. The AK0066690 transcript is expressed in the neonatal mouse heart but not in the neonatal brain, consistent with a model of silencing Ddc_exonla on the maternal allele via transcriptional interference. Ddc_exonla codes for the Dopa Decarboxylase (Ddc) protein, which is predominately expressed in the developing myocardium, this points to a role in fetal heart development. The role of Ddc in cardiogenesis is explored using knockout mice lacking Ddc_exonla expression in heart. Expression microarrays were used to detect changes in gene expression, and morphometric analysis using 3D imaging was performed to look for gross morphological changes. Results suggest that Ddc plays a role in regulating cellular proliferation and cardiogenesis of the developing myocardium as mice lacking Ddc show a significant thinning of the apical portion of the right ventricle, a region that shows abundant Ddc expression. In this thesis the significance of CTCF binding to imprinting control is examined and the observations applied in a locus specific manner to explore both the mechanistic control, and the functional role of Ddc in the developing mouse heart.
48
Rog-Zielinska, Eva Alicia. "Role of glucocorticoid signalling in fetal heart development and maturation." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/8086.
Full textAbstract:
Glucocorticoids are steroid hormones that affect a variety of physiological and pathological processes both throughout development and in adult life. During mammalian fetal growth, the late gestation rise in fetal glucocorticoid levels is essential for the maturation of tissues and organs in preparation for birth. In humans, glucocorticoids are routinely administered to women threatened by a preterm labour to accelerate fetal lung maturation and prevent neonatal respiratory distress and mice lacking glucocorticoid receptor (GR-/- mice) die neonatally as they are unable to inflate their lungs due to severe pulmonary immaturity. Apart from their importance for proper lung maturation, the physiological role of glucocorticoids in the development of other organs and tissues is not well known. However, prenatal exposure to excess glucocorticoids was shown to elicit detrimental “programming” effects, raising the susceptibility to adult diseases such as hypertension, obesity and metabolic disturbances in both humans and animal models. I therefore used global and conditional GR knock out mouse models to investigate the role and importance of adequate glucocorticoid signalling in fetal heart development and maturation. I further confirmed the direct effects of glucocorticoids on the cardiomyocyte structure and function in an in vitro setting. GR-/- fetuses are under-represented in late gestation (>50% of the number of GR+/+ littermates) but are present in the expected mendelian ratio at E14.5. At E17.5, GR-/- fetuses show edema (increased fluid accumulation and body sodium content). Excess extracellular fluid accumulation could be a result of a congenital heart failure. During development, corticosterone levels sharply increase within the fetal hearts at E15.5-E16.5, coincident with nuclear translocation of GR. Consistent with activation of GR only after this time, the phenotypic consequences of GR deficiency can be seen after E16.5 and not before. At E17.5, hearts of GR-/- fetuses are smaller than in GR+/+ but display no structural abnormalities. Cardiac function however is severely impaired, with left ventricular systolic and diastolic performance inferior in GR-/- fetuses compared to their wild-type littermates. Microscopically, at E17.5, the structure of the cardiac muscle and individual cardiomyocytes are affected by the lack of GR. The normal outer muscle layer, with characteristic rod-shaped, aligned cardiomyocytes is not discernable in the GR-/- heart. Within the cardiomyocytes, myofibrils are short, undefined and randomly scattered within the cell. Lack of the maturational progression in the GR-/- hearts at E17.5 is evident in the pattern of gene expression. GR-/- fetuses do not display the normal gestational changes between E14.5 and E17.5 that are seen in control mice, including in genes involved in the maturation of cardiac structure (eg myosin heavy chain-α, MyHC-α), function (atrial natriuretic peptide, ANP), energy metabolism (eg hexokinase-1, PPARγ coactivator-1α, PGC-1α) and calcium handling (ryanodine receptor, RyR; sarcoplasmic reticulum Ca2+-ATPase, SERCA2a). However, there are no genotype or gestational alterations in mRNA encoding the mineralocorticoid receptor, which is also a receptor for glucocorticoids in the heart. The normal gestational changes in the levels of modified histone H3 associated with the promoters of some of the genes (MyHC-α, ANP, PGC-1α) are not seen in hearts of GR-/- fetuses. This cardiac phenotype was not secondary to adrenal catecholamine insufficiency reported in other GR-/- models, as peripheral tissue levels of adrenaline were not different between genotypes. In order to test the hypothesis that the effects of glucocorticoids on the heart are mediated via GR in cardiomyocytes and to further elucidate the direct effects of GR deficiency specifically within the heart, mice with conditional deletion of GR selectively in cardiac and vascular smooth muscle cells were generated ("SMGRKO" mice). These show ~65% reduction in cardiac GR mRNA and protein levels. Circulating levels of corticosterone do not differ between genotypes at E17.5. SMGRKO fetuses at E17.5 display a phenotype strikingly similar to that of global GR-/-, namely edema, impaired cardiac function, impaired cellular architecture within the ventricle and alterations in the gene expression, implying that the GR-deficient phenotype is largely due to the direct actions of GR within the heart and not secondary to effects on other systems (eg kidney or liver). In order to investigate the pathways by which GR stimulates cardiomyocyte maturation, an in vitro model of murine primary fetal (E15.5-E16.5) cardiomyocytes was developed. Cultures contain >98% of troponin Tpositive cells which beat spontaneously. Treatment of cardiomyocytes with either synthetic (dexamethasone) or physiological (corticosterone) glucocorticoid induces time- and dose-dependent changes in gene expression, consistent with glucocorticoid-dependent changes seen in vivo in the late gestation heart. The effects of glucocorticoids on gene expression were abolished by either siRNA mediated knock-down of GR or RU486 antagonism of GR, but were unaffected by a mineralocorticoid receptor (MR) antagonist. Moreover, cycloheximide pretreatment (to block protein synthesis) suggested PGC-1α as a direct genomic target of GR. RNAseq transcriptome analysis performed on cardiomyocytes treated with dexamethasone and cycloheximide for 2h identified >600 genes as possible rapid and direct glucocorticoid response targets. Among them are genes involved in energy metabolism, calcium handling and sarcomere assembly. Glucocorticoid treatment of fetal cardiomyocytes also induces striking structural changes – formation of stress troponin T-associated actin fibers and sarcomere assembly. Spontaneous contractile activity is improved by glucocorticoid treatment, with a decrease in both contraction and relaxation time (without a change in frequency) and an improvement in the relaxation kinetics. In summary, glucocorticoid signalling in cardiomyocytes is required for the functional, structural and transcriptional maturation of the fetal heart in late gestation in vivo. Glucocorticoid treatment of primary murine fetal cardiomyocytes replicated the contractile, transcriptional and structural changes seen in vivo and was dependent on GR. Thus, GR is essential in cardiomyocytes for the structural and biochemical changes that underlie the maturation of heart function around the time of birth and an inadequate glucocorticoid environment could potentially lead to detrimental and permanent changes in postnatal cardiac function. Since prenatal glucocorticoids are routinely used clinically, it is important to consider any possible effects they might have on the heart development and its function later in life.
49
Jowett, Victoria Charlotte. "Brain growth and development in fetuses with congenital heart disease." Thesis, Imperial College London, 2017. http://hdl.handle.net/10044/1/49448.
Full textAbstract:
Introduction and Objectives: In the current era of excellent surgical results for congenital heart disease (CHD), focus has become directed on quality of life for these children. Previous studies have shown that neurodevelopmental outcome in CHD is impaired. The mechanisms are incompletely understood but there is increasing evidence that the origins of this are in fetal life. This thesis aims to describe the in utero brain growth in a cohort of fetuses with CHD and relate this to the circulatory abnormalities and fetal Doppler parameters. Methods: Pregnant women with a fetus with CHD were prospectively recruited. The congenital heart defect was phenotyped using fetal echocardiography and patients subdivided into three physiological groups on the basis of the anticipated abnormality of cerebral blood flow and oxygen delivery: (1) isolated reduced flow to the brain; 2) reduced oxygen saturation of cerebral blood flow; (3) combination of reduced oxygen and flow. Fetal brain MRI was performed. In addition to standard biometric measurements, snapshot to volume reconstruction (SVR) was used to construct a 3D data set from the oversampled raw data. From these 3D volumes the total brain volume and ventricular volumes were measured by manual segmentation. Serial measurements of fetal growth were also made and umbilical artery and middle cerebral artery Doppler parameters were analysed. Results: 29 women were included; comparison was made with 83 normal MRI controls. Fetuses with CHD were found to have smaller brain volumes compared to controls when adjusting for advancing gestation (p < 0.01). This difference becomes more pronounced with advancing gestation, suggesting a slower rate of in utero brain growth. Measurements of growth found that the fetuses with CHD were smaller throughout gestation with a highly significant difference at the later growth scan. (p < 0.001). Cerebral and umbilical artery Doppler data showed evidence of reduced cerebrovascular resistance in fetuses with CHD but did not show a difference in the umbilical artery Doppler. Conclusion: Fetuses with CHD have evidence of impaired brain growth with advancing pregnancy and an increased rate of overall growth restriction. Doppler evidence of cerebral vasodilation supports the mechanism of reduced oxygen delivery as an underlying cause.
50
Lodemore, Marion. "The development of temperature and heart rate rhythms in babies." Thesis, University of Leicester, 1993. http://hdl.handle.net/2381/34139.
Full text