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International Journal of Molecular... Dec 2021Insulin and Insulin-like growth factors (IGFs) perform key roles during embryonic development, regulating processes of cell proliferation and survival. The IGF... (Review)
Review
Insulin and Insulin-like growth factors (IGFs) perform key roles during embryonic development, regulating processes of cell proliferation and survival. The IGF signalling pathway comprises two IGFs (IGF1, IGF2), two IGF receptors (IGFR1, IGFR2), and six IGF binding proteins (IGFBPs) that regulate IGF transport and availability. The IGF signalling pathway is essential for cardiac development. IGF2 is the primary mitogen inducing ventricular cardiomyocyte proliferation and morphogenesis of the compact myocardial wall. Conditional deletion of the and the insulin receptor () genes in the myocardium results in decreased cardiomyocyte proliferation and ventricular wall hypoplasia. The significance of the IGF signalling pathway during embryonic development has led to consider it as a candidate for adult cardiac repair and regeneration. In fact, paracrine IGF2 plays a key role in the transient regenerative ability of the newborn mouse heart. We aimed to review the current knowledge about the role played by the IGF signalling pathway during cardiac development and also the clinical potential of recapitulating this developmental axis in regeneration of the adult heart.
Topics: Animals; Heart; Humans; Insulin-Like Growth Factor Binding Proteins; Morphogenesis; Myocardium; Receptor, IGF Type 1; Receptor, IGF Type 2; Regeneration; Signal Transduction; Somatomedins
PubMed: 35008660
DOI: 10.3390/ijms23010234 -
Journal of Cardiology Nov 2021The remodeling of the compact wall by incorporation of trabecular myocardium, referred to as compaction, receives much attention because it is thought that its failure... (Review)
Review
The remodeling of the compact wall by incorporation of trabecular myocardium, referred to as compaction, receives much attention because it is thought that its failure causes left ventricular non-compaction cardiomyopathy (LVNC). Although the notion of compaction is broadly accepted, the nature and strength of the evidence supporting this process is underexposed. Here, we review the literature that quantitatively investigated the development of the ventricular wall to understand the extent of compaction in humans, mice, and chickens. We queried PubMed using several search terms, screened 1127 records, and selected 56 publications containing quantitative data on ventricular growth. For humans, only 34 studies quantified wall development. The key premise of compaction, namely a reduction of the trabecular layer, was never documented. Instead, the trabecular layer grows slower than the compact wall in later development and this changes wall architecture. There were no reports of a sudden enlargement of the compact layer (from incorporated trabeculae), be it in thickness, area, or volume. Therefore, no evidence for compaction was found. Only in chickens, a sudden increase in compact myocardial thickness layer was reported coinciding with a decrease in trabecular thickness. In mice, morphometric and lineage tracing investigations have yielded conflicting results that allow for limited compaction to occur. In conclusion, compaction in human development is not supported while rapid intrinsic growth of the compact wall is supported in all species. If compaction takes place, it likely plays a much smaller role in determining wall architecture than intrinsic growth of the compact wall.
Topics: Animals; Chickens; Heart Ventricles; Humans; Isolated Noncompaction of the Ventricular Myocardium; Mice; Myocardium
PubMed: 33840532
DOI: 10.1016/j.jjcc.2021.03.006 -
European Journal of Sport Science Nov 2017The aim of the present study was to compare cardiac structure as well as global and regional cardiac function in athletes with and without myocardial fibrosis (MF)....
The aim of the present study was to compare cardiac structure as well as global and regional cardiac function in athletes with and without myocardial fibrosis (MF). Cardiac magnetic resonance imaging with late gadolinium enhancement was used to detect MF and global cardiac structure in nine lifelong veteran endurance athletes (58 ± 5 years, 43 ± 5 years of training). Transthoracic echocardiography using tissue-Doppler and myocardial strain imaging assessed global and regional (18 segments) longitudinal left ventricular function. MF was present in four athletes (range 1-8 g) and not present in five athletes. MF was located near the insertion points of the right ventricular free wall on the left ventricle in three athletes and in the epicardial lateral wall in one athlete. Athletes with MF demonstrated a larger end diastolic volume (205 ± 24 vs 173 ± 18 ml) and posterior wall thickness (11 ± 1 vs 9 ± 1 mm) compared to those without MF. The presence of MF did not mediate global tissue velocities or global longitudinal strain and strain rate; however, regional analysis of longitudinal strain demonstrated reduced function in some fibrotic regions. Furthermore, base to apex gradient was affected in three out of four athletes with MF. Lifelong veteran endurance athletes with MF demonstrate larger cardiac dimensions and normal global cardiac function. Fibrotic areas may demonstrate some co-localised regional cardiac dysfunction, evidenced by an affected cardiac strain and base to apex gradient. These data emphasize the heterogeneous phenotype of MF in athletes.
Topics: Aged; Athletes; Echocardiography; Fibrosis; Heart; Heart Diseases; Humans; Middle Aged; Myocardium; Stroke Volume; Ventricular Function, Left
PubMed: 28910586
DOI: 10.1080/17461391.2017.1373864 -
Journal of Medical Ultrasonics (2001) Oct 2022Because the posterior wall of the aorta and left atrium are interlocked, the amplitude of motion of the aortic wall (AMAW) may reflect cardiac and vessel functions. This...
PURPOSE
Because the posterior wall of the aorta and left atrium are interlocked, the amplitude of motion of the aortic wall (AMAW) may reflect cardiac and vessel functions. This study examined the relationship between cardiac and vessel functions and AMAW.
METHODS
Patients with cardiovascular diseases or patients undergoing health examinations who visited a participating hospital and underwent echocardiography and brachial-ankle pulse-wave velocity (baPWV) examinations were registered. The correlations between echocardiographic indices, ankle-brachial index, and baPWV and AMAW on M-mode echocardiography were analyzed.
RESULTS
Overall, 184 patients were enrolled. Heart rate (r = - 0.1587), ejection fraction (EF; r = 0.3240), wall thickness (r = - 0.1598), peak early diastolic mitral annular velocity (E) to peak early diastolic mitral annular velocity ratio (e'; r = - 0.2463), and baPWV (r = - 0.1928) significantly correlated with AMAW. In the stratified multiple regression analysis, E/e' (standardized partial regression coefficients = - 0.1863) and mean baPWV (standardized partial regression coefficients = - 0.1917) in patients with an EF of ≥ 60% (n = 114) significantly correlated with AMAW. In patients with an EF of < 60% (n = 70), E/e' (standardized partial regression coefficients = - 0.2443) significantly correlated with AMAW.
CONCLUSION
Because E/e' correlated with AMAW in patients with an EF of < 60% or ≥ 60%, AMAW might be an indicator of left atrial pressure elevation. Moreover, because AMAW correlated with baPWV in patients with an EF of ≥ 60%, changes in the restricted left atrial volume might influence diastolic dysfunction. AMAW may be related to cardiac and vessel functions.
Topics: Humans; Aorta; Echocardiography; Pulse Wave Analysis; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left; Heart
PubMed: 35840775
DOI: 10.1007/s10396-022-01238-y -
American Journal of Medical Genetics.... Aug 2013Congenital heart diseases are some of the most common human birth defects. Though some congenital heart defects can be surgically corrected, treatment options for other... (Review)
Review
Congenital heart diseases are some of the most common human birth defects. Though some congenital heart defects can be surgically corrected, treatment options for other congenital heart diseases are very limited. In many congenital heart diseases, genetic defects lead to impaired embryonic heart development or growth. One of the key development processes in cardiac development is chamber maturation, and alterations in this maturation process can manifest as a variety of congenital defects including non-compaction, systolic dysfunction, diastolic dysfunction, and arrhythmia. During development, to meet the increasing metabolic demands of the developing embryo, the myocardial wall undergoes extensive remodeling characterized by the formation of muscular luminal protrusions called cardiac trabeculae, increased cardiomyocyte mass, and development of the ventricular conduction system. Though the basic morphological and cytological changes involved in early heart development are clear, much remains unknown about the complex biomolecular mechanisms governing chamber maturation. In this review, we highlight evidence suggesting that a wide variety of basic signaling pathways and biomechanical forces are involved in cardiac wall maturation.
Topics: Biomechanical Phenomena; Cell Proliferation; Fetal Heart; Heart Conduction System; Heart Defects, Congenital; Humans; Myocytes, Cardiac; Signal Transduction
PubMed: 23720419
DOI: 10.1002/ajmg.c.31366 -
IEEE Journal of Biomedical and Health... Jul 2021Quantitative assessment of cardiac left ventricle (LV) morphology is essential to assess cardiac function and improve the diagnosis of different cardiovascular diseases....
Quantitative assessment of cardiac left ventricle (LV) morphology is essential to assess cardiac function and improve the diagnosis of different cardiovascular diseases. In current clinical practice, LV quantification depends on the measurement of myocardial shape indices, which is usually achieved by manual contouring of the endo- and epicardial. However, this process subjected to inter and intra-observer variability, and it is a time-consuming and tedious task. In this article, we propose a spatio-temporal multi-task learning approach to obtain a complete set of measurements quantifying cardiac LV morphology, regional-wall thickness (RWT), and additionally detecting the cardiac phase cycle (systole and diastole) for a given 3D Cine-magnetic resonance (MR) image sequence. We first segment cardiac LVs using an encoder-decoder network and then introduce a multitask framework to regress 11 LV indices and classify the cardiac phase, as parallel tasks during model optimization. The proposed deep learning model is based on the 3D spatio-temporal convolutions, which extract spatial and temporal features from MR images. We demonstrate the efficacy of the proposed method using cine-MR sequences of 145 subjects and comparing the performance with other state-of-the-art quantification methods. The proposed method obtained high prediction accuracy, with an average mean absolute error (MAE) of 129 mm , 1.23 mm, 1.76 mm, Pearson correlation coefficient (PCC) of 96.4%, 87.2%, and 97.5% for LV and myocardium (Myo) cavity regions, 6 RWTs, 3 LV dimensions, and an error rate of 9.0% for phase classification. The experimental results highlight the robustness of the proposed method, despite varying degrees of cardiac morphology, image appearance, and low contrast in the cardiac MR sequences.
Topics: Heart; Heart Ventricles; Humans; Magnetic Resonance Imaging; Magnetic Resonance Imaging, Cine; Radiography
PubMed: 33351771
DOI: 10.1109/JBHI.2020.3046449 -
Biochimica Et Biophysica Acta Apr 2013At the end of the first week of mouse gestation, cardiomyocyte differentiation initiates in the cardiac crescent to give rise to the linear heart tube. The heart tube... (Review)
Review
At the end of the first week of mouse gestation, cardiomyocyte differentiation initiates in the cardiac crescent to give rise to the linear heart tube. The heart tube subsequently elongates by addition of cardiac progenitor cells from adjacent pharyngeal mesoderm to the growing arterial and venous poles. These progenitor cells, termed the second heart field, originate in splanchnic mesoderm medial to cells of the cardiac crescent and are patterned into anterior and posterior domains adjacent to the arterial and venous poles of the heart, respectively. Perturbation of second heart field cell deployment results in a spectrum of congenital heart anomalies including conotruncal and atrial septal defects seen in human patients. Here, we briefly review current knowledge of how the properties of second heart field cells are controlled by a network of transcriptional regulators and intercellular signaling pathways. Focus will be on 1) the regulation of cardiac progenitor cell proliferation in pharyngeal mesoderm, 2) the control of progressive progenitor cell differentiation and 3) the patterning of cardiac progenitor cells in the dorsal pericardial wall. Coordination of these three processes in the early embryo drives progressive heart tube elongation during cardiac morphogenesis. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.
Topics: Animals; Cell Differentiation; Cell Proliferation; Embryo, Mammalian; Gene Expression Regulation; Heart; Mesoderm; Mice; Myocytes, Cardiac; Myogenic Regulatory Factors; Organogenesis; Signal Transduction; Stem Cells; T-Box Domain Proteins; Transcription, Genetic
PubMed: 23051926
DOI: 10.1016/j.bbamcr.2012.10.003 -
Journal of the American Society of... May 2018Cardiovascular disease is the leading cause of mortality in patients receiving hemodialysis. Cardiovascular events in these patients demonstrate a day-of-week pattern;... (Review)
Review
Cardiovascular disease is the leading cause of mortality in patients receiving hemodialysis. Cardiovascular events in these patients demonstrate a day-of-week pattern; they occur more commonly during the last day of the long interdialytic interval and the first session of the week. The hemodialysis process causes acute decreases in cardiac chamber size and pulmonary circulation loading and acute diastolic dysfunction, possibly through myocardial stunning and other non-myocardial-related mechanisms; systolic function, in contrast, is largely unchanged. During interdialytic intervals volume overload, acid-base, and electrolyte shifts, as well as arterial and myocardial wall changes, result in dilatation of right cardiac chambers and pulmonary circulation overload. Recent studies suggest that these alterations are more extended during the long interdialytic interval or the first dialysis session of the week and are associated with excess volume overload or removal, respectively, thus adding a mechanism for the day-of-week pattern of mortality in patients receiving hemodialysis. This review summarizes the existing data from echocardiographic studies of cardiac morphology and function during the hemodialysis session, as well as during the interdialytic intervals.
Topics: Diastole; Echocardiography; Heart; Humans; Kidney Failure, Chronic; Renal Dialysis; Systole
PubMed: 29592914
DOI: 10.1681/ASN.2017101102 -
Cardiovascular Engineering and... Oct 2022External cardiac assist devices are based on a promising and simple concept for treating heart failure, but they are surprisingly difficult to design. Thus, a structured...
PURPOSE
External cardiac assist devices are based on a promising and simple concept for treating heart failure, but they are surprisingly difficult to design. Thus, a structured approach combining experiments with computer-based optimization is essential. The latter provides the motivation for the work presented in this paper.
METHODS
We present a computational modeling framework for realistic representation of the heart's tissue structure, electrophysiology and actuation. The passive heart tissue is described by a nonlinear anisotropic material law, considering fiber and sheetlet directions. For muscle contraction, an orthotropic active-strain model is employed, initiated by a periodically propagating electrical potential. The model allows for boundary conditions at the epicardium accounting for external assist devices, and it is coupled to a circulation network providing appropriate pressure boundary conditions inside the ventricles.
RESULTS
Simulated results from an unsupported healthy and a pathological heart model are presented and reproduce accurate deformations compared to phenomenological measurements. Moreover, cardiac output and ventricular pressure signals are in good agreement too. By investigating the impact of applying an exemplary external actuation to the pathological heart model, it shows that cardiac patches can restore a healthy blood flow.
CONCLUSION
We demonstrate that the devised computational modeling framework is capable of predicting characteristic trends (e.g. apex shortening, wall thickening and apex twisting) of a healthy heart, and that it can be used to study pathological hearts and external activation thereof.
Topics: Humans; Heart-Assist Devices; Models, Cardiovascular; Heart; Heart Ventricles; Heart Failure; Computer Simulation
PubMed: 35292915
DOI: 10.1007/s13239-022-00610-w -
Annual Review of Pathology May 2016Cardiac developmental disorders represent the most common of human birth defects, and anomalies in cardiomyocyte proliferation drive many of these disorders. This review... (Review)
Review
Cardiac developmental disorders represent the most common of human birth defects, and anomalies in cardiomyocyte proliferation drive many of these disorders. This review highlights the molecular mechanisms of prenatal cardiac growth. Trabeculation represents the initial ventricular growth phase and is necessary for embryonic survival. Later in development, the bulk of the ventricular wall derives from the compaction process, yet the arrest of this process can still be compatible with life. Cardiomyocyte proliferation and growth form the basis of both trabeculation and compaction, and mouse models indicate that cardiomyocyte interactions with the surrounding environment are critical for these proliferative processes. The human genetics of left ventricular noncompaction cardiomyopathy suggest that cardiomyocyte cell-autonomous mechanisms contribute to the compaction process. Understanding the determinants of prenatal or early postnatal cardiomyocyte proliferation and growth provides critical information that identifies risk factors for cardiovascular disease, including heart failure and its associated complications of arrhythmias and thromboembolic events.
Topics: Animals; Cell Proliferation; Disease Models, Animal; Heart Failure; Heart Ventricles; Humans; Myocytes, Cardiac
PubMed: 26925501
DOI: 10.1146/annurev-pathol-012615-044336