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Results for “Heart development”

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At least 217 records · Page 12Linked to original sources
PubMed2000

Trk C receptor signaling regulates cardiac myocyte proliferation during early heart development in vivo.

Neurotrophin-3 (NT-3) is a member of the neurotrophin family of growth factors, best characterized by its survival- and differentiation-inducing effects on developing neurons bearing the trk C receptor tyrosine kinase. Through analysis of NT-3 and trk C gene-targeted mice we have identified NT-3 as critically regulating cardiac septation, valvulogenesis, and conotruncal formation. Although these defects could reflect cardiac neural crest dysfunction, the expression of NT-3 and trk C by cardiac myocytes prior to neural crest migration prompted analysis of cell-autonomous actions of NT-3 on cardiac myocytes. Retroviral-mediated overexpression of truncated trk C receptor lacking kinase activity was used to inhibit activation of trk C by endogenous NT-3, during early heart development in ovo. During the first week of chicken development, expression of truncated trk C reduced myocyte clone size by more than 60% of control clones. Direct mitogenic actions of NT-3 on embryonic cardiac myocytes were demonstrated by analysis of BrdU incorporation or PCNA immunoreactivity in control and truncated trk C-expressing clones. Inhibition of trk C signaling reduced cardiac myocyte proliferation during the first week of development, but had no effect at later times. These studies demonstrate that endogenous NT-3:trk C signaling regulates cardiac myocyte proliferation during cardiac looping and the establishment of ventricular trabeculation but that myocyte proliferation becomes NT-3 independent during the second week of embryogenesis.

Amino Acid Sequence↗
PubMed2004

Combined inhibition of angiotensin II and endothelin suppresses the brain natriuretic peptide response to developing heart failure.

Blockade of AngII (angiotensin II) and ET (endothelin)-1, established and potential therapeutic strategies respectively, for heart failure, may have an adverse effect on the cardiac secretion of the natriuretic peptides, hormones with actions beneficial in this disease. The present study investigates the roles of AngII and ET-1 in regulating the stretch-induced release of the natriuretic peptides during the development of heart failure. On seven separate days, eight sheep underwent incremental left ventricular pacing (155, 190 and 225 beats/min for 90 min each) with concurrent infusions of a vehicle control, AngII, ET-1, AngII+ET-1, losartan [AT1 (AngII type 1) receptor antagonist], bosentan (ET(A)/ET(B) receptor antagonist) or losartan+bosentan. Pacing-induced rises in LAP (left atrial pressure) were amplified by the simultaneous administration of separate AngII and ET-1, and attenuated following blockade of the peptides, with maximum effects observed during combined treatments. Although these changes in atrial pressure were paralleled by concomitant alterations in circulating levels of both ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide), the plasma natriuretic peptide/atrial pressure relationship tended to be augmented by AngII and ET-1 and diminished by their blockade. A significant difference was demonstrated between the enhanced plasma BNP response to increasing LAP during combined AngII+ET-1 administration and decreased response during losartan+bosentan treatment ( P <0.05). A similar, but non-significant, trend was evident for ANP. The present study indicates dual AngII/ET-1 blockade diminishes BNP (and to a lesser extent ANP) secretion in developing heart failure, suggesting that augmentation of the natriuretic peptide system during the combination of these therapies may be of benefit.

Angiotensin II↗
PubMed2003

Effects of pulmonary insufficiency on biventricular function in the developing heart of growing swine.

BACKGROUND: This study was conducted to determine the effects of chronic pulmonary insufficiency (PI) on right (RV) and left (LV) ventricular function in young growing swine. METHODS AND RESULTS: Six PI and 5 control animals were studied. PI was induced by transcatheter placement of stents across the pulmonary valve. Indices of systolic function (ejection fraction, cardiac output, and cardiac functional reserve), diastolic function (compliance), and myocardial contractility (the slope of the relationship of end-systolic pressure versus end-systolic volume [Emax] and the slope of the dP/dtmax-end-diastolic volume relationship [MdP/dt]) were assessed within 2 days of intervention and 3 months later. MRI was used to quantify PI and ventricular volumes. Conductance catheter techniques were used to obtain indices of contractility and diastolic compliance from pressure-volume relations at rest and under dobutamine infusion. In the PI group, pulmonary regurgitant fraction was 49.2+/-5.9% at 3-month follow-up. RV cardiac functional reserve was limited, diastolic function was preserved, and myocardial contractility was altered (Emax=2.6+/-0.3 mm Hg/mL for the PI group versus 3.5+/-0.4 mm Hg/mL for control; P<0.01). LV cardiac functional reserve was limited, ventricular compliance decreased, and myocardial contractility was preserved. CONCLUSIONS: In the young developing heart, chronic PI alters biventricular systolic function, RV myocardial contractility, and LV diastolic performance.

Animals↗
PubMed2005

Combined pulmonary stenosis and insufficiency preserves myocardial contractility in the developing heart of growing swine at midterm follow-up.

This study was conducted to determine the effects of chronic combined pulmonary stenosis and pulmonary insufficiency (PSPI) on right (RV) and left ventricular (LV) function in young, growing swine. Six pigs with combined PSPI were studied, and data were compared with previously published data of animals with isolated pulmonary insufficiency and controls. Indexes of systolic function (stroke volume, ejection fraction, and cardiac functional reserve), myocardial contractility (slope of the end-systolic pressure-volume and change in pressure over time-end-diastolic volume relationship), and diastolic compliance were assessed within 2 days of intervention and 3 mo later. Magnetic resonance imaging was used to quantify pulmonary insufficiency and ventricular volumes. The conductance catheter was used to obtain indexes of the cardiac functional reserve, diastolic compliance, and myocardial contractility from pressure-volume relations acquired at rest and under dobutamine infusion. In the PSPI group, the pulmonary regurgitant fraction was 34.3 +/- 5.8%, the pressure gradient across the site of pulmonary stenosis was 20.9 +/- 20 mmHg, and the average RV peak systolic pressure was 70% systemic at 12 wk follow-up. Biventricular resting cardiac outputs and cardiac functional reserves were significantly limited (P < 0.05), LV diastolic compliance significantly decreased (P < 0.05), but RV myocardial contractility significantly enhanced (P < 0.05) compared with control animals at 3-mo follow-up. In the young, developing heart, chronic combined PSPI impairs biventricular systolic pump function and diastolic compliance but preserves RV myocardial contractility.

Aging↗
PubMed1999

Signal transduction and transcriptional adaptation in embryonic heart development and during myocardial hypertrophy.

In comparing the pathological state of cardiac hypertrophy with early embryonic growth and development of the primitive heart, important and informative aspects of mechanisms that underlie activation of the gene expression pattern become apparent. Interestingly, in both cases the muscle phenotypes share the expression of a 'fetal' gene expression program, raising the question whether the same genetic mechanism is being called upon by signals associated with the onsets of cardiogenesis and myocardial hypertrophy. A cell specific transcription factor, CLP-1, was recently identified in our laboratory that is likely to play a crucial role, in conjunction with other known regulatory factors, in early cardiac events leading to cardiogenic cell specification and differentiation. We have also identified a novel mechanism that involves activation of the Jak/Stat signaling pathway that is linked to the autocrine angiotensin-II loop associated with the hypertrophic response in cardiomyocytes. Since early cardiac cell development and the hypertrophic state involve the expression of the same battery of genes, one may speculate that common transcription factors may account for assembling a competent apparatus responsible for transcribing the genes. Our present studies are designed to investigate the potential role of these factors in control of both processes.

Adaptation, Physiological↗
PubMedDate not supplied

Protein kinase C zeta regulation of hypertrophic and apoptotic events occurring during rat neonatal heart development and growth.

The development and growth of the rat heart implies hyperplasia, which stops at birth, and hypertrophy, allowing cardiac mass to grow in response to programmed genetic events along with to haemodynamic overload. Moreover, hypertrophy is accomplished to apoptosis which controls the final number of myocardial cells, deletes vestigial structures, and takes part in remodelling the organ. Since at the basis of all these processes, which lead to the complete development of the heart, the activation of specific signalling pathways underlies, attention has been addressed to the role played in vivo by Protein Kinase C zeta (PKC zeta) in regulating NF-kB signalling system and intrinsic mitochondrial apoptotic route at days 1, 4, 10 and 22 of rat life. In fact, a role has been assigned to PKC zeta in indirectly phosphorylating IKBa, which peaks between 10 and 22 days, through a IKK determining, in turn, NF-kB activation, concomitantly to cytochrome c/Apaf 1 co-localization in the cytoplasm and caspase-9/caspase-3 activation, which leads to the occurrence of apoptosis. Thus a key role for PKC zeta in regulating the hypertrophic and apoptotic events leading to establishment of complete function in rat neonatal heart is here suggested.

Animals↗
PubMed2025

How to Study Gene Expression and Gain of Function of Hoxb1 in Mouse Heart Development.

Anterior Hox genes are required for genetic identity and anterior posterior patterning of the second heart field (SHF), which contributes to the formation of the embryonic heart in vertebrates. Defective contribution of SHF cells to the arterial or venous pole of the heart is often associated with severe congenital heart defects. The mouse Cre-lox system allows the activation of expression of any gene of interest in restricted tissues. We developed a gain of function approach that relies on the use of a CAG transgene to ectopically activate Hoxb1 expression in SHF cardiac progenitor cells through specific Cre activation. Therefore, we generated a floxed transgenic mouse line, CAG-Hoxb1-eGFP, which upon recombination by Cre recombinase conditionally induces robust Hoxb1 and eGFP expression. When induced within the anterior SHF lineage, we detected heart defects in mouse embryos such as right ventricular hypoplasia. Here, we describe the strategy for generating and genetically crossing this transgenic mouse line. We also provide detailed protocols for whole-mount embryo and paraffin section in situ RNAscope hybridization and X-gal staining allowing investigation of SHF contribution during heart development.

Animals↗
PubMed2002

Theoretical and experimental study of growth and remodeling in the developing heart.

A theoretical model is presented for growth and remodeling in the developing embryonic heart. The model is a thick-walled tube composed of two layers of orthotropic pseudoelastic material. The analysis includes stress and strain dependent volumetric growth, with changes in material properties specified to reflect the evolving structure of the heart wall. For use in model validation, experimental measurements of ventricular opening angles are reported for 3-4-day old chick embryos under control and pressure overload conditions. Owing to changes in residual stress in the overloaded heart, the opening angle decreased from 31 +/- 10 degrees to -8 +/- 12 degrees (mean +/- SD) within 12 h and then increased slightly. The opening angle at 12 h was significantly less than the control value. With an appropriate choice of parameters, the model yields reasonable agreement with these and other published opening angle data, as well as with temporal changes in lumen radius, wall thickness, epicardial strains, and pressure-volume curves during development before and after birth.

Animals↗
PubMed1983

An analysis of contractile proteins in developing chick heart by SDS polyacrylamide gel electrophoresis and electron microscopy.

Chick heart development was studied using transmission electron microscopy and SDS-polyacrylamide gel electrophoresis in combination with densitometry. Myosin heavy chain, alpha-actinin, actin and tropomyosin accumulations were analysed in developing hearts from preheartbeat stage 9 (Hamburger-Hamilton staging series) through 2 days after hatching. At the preheartbeat stage, electron microscopy revealed a significant number of thin filaments scattered throughout the cytoplasm of the myoblasts; however, very few thick filaments were seen. There was no obvious association between the two filament types. SDS-polyacrylamide tube gels of heart muscle homogenates demonstrated the presence of all five proteins in hearts at the preheartbeat stage. Further analyses of the proteins by gel densitometry indicated that both actin and myosin accumulated rapidly during heart development while alpha-actinin and tropomyosin levels remained relatively static. Our results show that detectable quantities of myosin heavy chain, alpha-actinin, actin and tropomyosin accumulate in myocardial cells prior to the appearance of myofibrils and initiation of the contractile function.

Actinin↗
PubMed2006

Chromatin modification and remodeling in heart development.

In organogenesis, cell types are specified from determined precursors as morphogenetic patterning takes place. These events are largely controlled by tissue-specific transcription factors. These transcription factors must function within the context of chromatin to activate or repress target genes. Recent evidence suggests that chromatin-remodeling and -modifying factors may have tissue-specific function. Here we review the potential roles for chromatin-remodeling and -modifying proteins in the development of the mammalian heart.

Animals↗
PubMedDate not supplied

Method of noninvasive and continuous hemolysis/thrombogenesis measurement by laser photometry during artificial heart development.

The purpose of this research is to propose and develop a method to measure hemolysis and thrombogenesis non invasively and continuously to aid in development of an artificial heart. Generally, the optical absorption rate of hemoglobin is influenced by oxygen saturation except at the isosbestic point, which is not influenced by oxygen saturation. The authors, therefore, used an 805 nm laser diode, an optical spectrum analyzer to obtain greater accuracy. An experimental blood circuit system was constructed using a Bio-Pump, Tygon tubing, a soft shell reservoir, and an optical measurement system. Experimental settings for monitoring hemolysis were as follows; blood volume 200 ml, blood flow 6 L/min, and afterload 200 mmHg. Blood was sampled six times (0, 30, 60, 120, 180, and 240 min), and hemolysis in each sampled was measured using a colorimetric method. Comparing continuous laser measurement data with the sample data, an adequate correlation is obtained, proving that the dynamic trend of hemolysis could be continuously measured. Furthermore, to analyze the process of thrombogenesis, simple experiments were performed using blood neutralized by protamine. As a result, the authors could see the process of thrombogenesis as it occurred and could confirm that this method is able to dynamically detect hemolysis and thrombogenesis.

Biomedical Engineering↗
PubMed1999

The cardiac expression of striated muscle LIM protein 1 (SLIM1) is restricted to the outflow tract of the developing heart.

LIM proteins perform critical roles in development and tissue differentiation. The skeletal muscle LIM protein 1 (SLIM1) comprises four and a half LIM domains. Northern blot analysis demonstrated high level expression of SLIM1 mRNA in adult human skeletal muscle with intermediate expression in adult heart and lower expression in other tissues. Western blot analysis using specific affinity-purified anti-SLIM1 antipeptide antibodies demonstrated a 32 kDa polypeptide in the aorta and atria of rabbit heart, but not in vena cava, interventricular septum or ventricular muscle. SLIM1 was also demonstrated in rabbit skeletal muscle. In situ hybridization of whole mouse embryos confirmed the cardiac expression of SLIM1 was restricted to the cardiac outflow tract from embryonic day 8.5-11. No expression was seen in atrial or ventricular muscle. SLIM1 mRNA was also demonstrated in the hindbrain, neural tube and somites. The localized expression of SLIM1 to the outflow tract of the embryonic heart implies an important role for the protein in the development of this region and possibly in congenital heart anomalies involving the separation and formation of the aortic and pulmonary trunks.

Adult↗
PubMed1983

Experimental results for chronic left ventricular assist and total artificial heart development.

After more than 20 years of research on the artificial heart, it is now accepted that the pneumatically actuated total artificial heart can maintain near-normal physiology in experimental animals for several months. Such systems are clinically acceptable for short-term application (a few months) in patients waiting for a suitable heart transplant. However, realistically, a cardiac prosthesis that has the capability of being totally implantable for over 2 years must be available. Based on this premise, our group initiated the development of a mechanically actuated total artificial heart, capable of coupling with either a thermal or electrical actuation system. Since 1977, under the National Institutes of Health chronic left ventricular assist program, we have used two different pusher-plate pumps and electrical systems. Taking advantage of technology generated in these programs, we began developing a prosthesis to replace the total cardiac function. This paper is a summary of both the chronic left ventricular assist and total artificial heart development progress in this laboratory.

Animals↗
PubMed2001

Regulation of heart development and function through combinatorial interactions of transcription factors.

Understanding the molecular mechanisms controlling cardiac-specific gene transcription requires the dissection of the cis-elements that govern the complex spatio-temporal expression of these genes. The four-chambered vertebrate heart is formed during the late phases of fetal development following a series of complex morphogenetic events that require the functional presence of different proteins. The gradient-like expression of some genes, as well as the chamber-specific expression of others, is tightly regulated by combinatorial interactions of several transcription factors and their cofactors. Chamber- and stage-specific cardiac myocyte cultures have been invaluable for identifying transcription factor binding sites involved in basal, chamber-specific, and inducible expression of many cardiac promoters; these studies, which were largely confirmed in vivo in transgenic mouse models, led to the isolation of key regulators of heart development. In addition, the use of pluripotent embryonic stem cells helped elucidate the early molecular events controlling cardiomyocyte differentiation. Together, these studies point to a major role for GATA transcription factors and their interacting partners in transcriptional control of heart development. In addition, members of the T-box family of transcription factors and homeodomain containing proteins, together with chamber-restricted transcriptional repressors and co-repressors play critical roles in heart septation and chamber specification. These fine-tuned cooperative interactions between different classes of proteins are at the basis of normal cardiac function, and alteration in their expression level or function leads to cardiac pathologies.

Animals↗
PubMed2000

Genetics of heart development.

The genes that drive heart-cell differentiation in vertebrates and Drosophila are similar, even though the Drosophila 'heart' is a simple tube and the vertebrate heart is a multichambered physiologically complex organ. Mutational analysis in mice and, as particular focus of this review, in zebrafish, reveals the additional genes brought into play to fashion these evolutionarily 'new' organotypic components.

Animals↗
PubMed2006

Maintenance of the metabolic homeostasis of the heart: developing a systems analysis approach.

The heart is almost unique in the body with a constant requirement to conduct work well beyond the normal maintenance of cellular integrity. With this constant workload, it is not surprising that cardiac energy conversion is highly specialized to maintain a constant supply of energy. This maintenance of cellular metabolites during alterations in workload has been termed metabolic homeostasis. Here we discuss our efforts to understand the cellular and mitochondrial control network that orchestrates the metabolic homeostasis of the heart. This begins with a better definition of the metabolic pathways, acute posttranslational control sites, and proper kinetic evaluation of the reaction steps in the intact mitochondrial environment. First, a quantitative model of mitochondrial energy conversion is presented and demonstrates several serious gaps in our knowledge of this process. Toward filling these gaps, screens of the entire mitochondrial proteome have been conducted to establish the metabolic pathways that need to be considered. In addition, the dynamic phosphoproteome of intact mitochondria, using 2D gel electrophoresis coupled to (32)P labeling, has revealed a remarkably extensive protein phosphorylation network throughout the mitochondrial metabolic network that has essentially been overlooked. Initial studies on evaluating the functional significance of these protein phosphorylations and the kinase-phosphatase system involved will be reviewed. One of the major deficits in the consensus quantitative model of oxidative phosphorylation to explain intact mitochondria activities is in complex I, where even the initiation of Nicotinamide Adenine Dinucleotide (reduced) (NADH) oxidation is problematical using in vitro kinetic data. Studies will be described where the NADH binding and oxidation kinetics at complex I in the intact mitochondria were determined using fluorescence lifetime and enzyme dependent-fluorescence recovery after photo-oxidation (ED-FRAP) techniques. These later studies suggest that matrix NADH binding characteristics are much different (>10(3) binding constant errors) than isolated proteins. In addition, complex I is far from equilibrium and may play an important role in regulating the rate of reducing equivalent delivery to the cytochromes.

Animals↗