-
Circulation Research Jul 2022Establishment of the myocardial wall requires proper growth cues from nonmyocardial tissues. During heart development, the epicardium and epicardium-derived cells...
BACKGROUND
Establishment of the myocardial wall requires proper growth cues from nonmyocardial tissues. During heart development, the epicardium and epicardium-derived cells instruct myocardial growth by secreting essential factors including FGF (fibroblast growth factor) 9 and IGF (insulin-like growth factor) 2. However, it is poorly understood how the epicardial secreted factors are regulated, in particular by chromatin modifications for myocardial formation. The current study is to investigate whether and how HDAC (histone deacetylase) 3 in the developing epicardium regulates myocardial growth.
METHODS
Various cellular and mouse models in conjunction with biochemical and molecular tools were employed to study the role of HDAC3 in the developing epicardium.
RESULTS
We deleted in the developing murine epicardium, and mutant hearts showed ventricular myocardial wall hypoplasia with reduction of epicardium-derived cells. The cultured embryonic cardiomyocytes with supernatants from knockout (KO) mouse epicardial cells also showed decreased proliferation. Genome-wide transcriptomic analysis revealed that and were significantly downregulated in KO mouse epicardial cells. We further found that and expression is dependent on HDAC3 deacetylase activity. The supplementation of FGF9 or IGF2 can rescue the myocardial proliferation defects treated by KO supernatant. Mechanistically, we identified that microRNA (miR)-322 and miR-503 were upregulated in KO mouse epicardial cells and epicardial KO hearts. Overexpression of miR-322 or miR-503 repressed FGF9 and IGF2 expression, while knockdown of miR-322 or miR-503 restored FGF9 and IGF2 expression in KO mouse epicardial cells.
CONCLUSIONS
Our findings reveal a critical signaling pathway in which epicardial HDAC3 promotes compact myocardial growth by stimulating FGF9 and IGF2 through repressing miR-322 or miR-503, providing novel insights in elucidating the etiology of congenital heart defects and conceptual strategies to promote myocardial regeneration.
Topics: Animals; Heart; Mice; MicroRNAs; Myocardium; Myocytes, Cardiac; Pericardium; Signal Transduction
PubMed: 35722872
DOI: 10.1161/CIRCRESAHA.122.320785 -
Herzschrittmachertherapie &... Sep 2022To understand the position of a pacing lead in the right ventricle and to correctly interpret fluoroscopy and intracardiac signals, good anatomical knowledge is... (Review)
Review
To understand the position of a pacing lead in the right ventricle and to correctly interpret fluoroscopy and intracardiac signals, good anatomical knowledge is required. The right ventricle can be separated into an inlet, an outlet, and an apical compartment. The inlet and outlet are separated by the septomarginal trabeculae, while the apex is situated below the moderator band. A lead position in the right ventricular apex is less desirable, last but not least due to the thin myocardial wall. Many leads supposed to be implanted in the apex are in fact fixed rather within the trabeculae in the inlet, which are sometimes difficult to pass. In the right ventricular outflow tract (RVOT), the free wall is easier to reach than the septal due to the fact that the RVOT wraps around the septum. A mid-septal position close to the moderator band is relatively simple to achieve and due to the vicinity of the right bundle branch may produce a narrower paced QRS complex. Special and detailed knowledge is necessary for His bundle and left bundle branch pacing.
Topics: Cardiac Pacing, Artificial; Electrocardiography; Heart Conduction System; Heart Ventricles; Humans; Ventricular Septum
PubMed: 35763099
DOI: 10.1007/s00399-022-00872-w -
Nature Mar 2024The heart, which is the first organ to develop, is highly dependent on its form to function. However, how diverse cardiac cell types spatially coordinate to create the...
The heart, which is the first organ to develop, is highly dependent on its form to function. However, how diverse cardiac cell types spatially coordinate to create the complex morphological structures that are crucial for heart function remains unclear. Here we integrated single-cell RNA-sequencing with high-resolution multiplexed error-robust fluorescence in situ hybridization to resolve the identity of the cardiac cell types that develop the human heart. This approach also provided a spatial mapping of individual cells that enables illumination of their organization into cellular communities that form distinct cardiac structures. We discovered that many of these cardiac cell types further specified into subpopulations exclusive to specific communities, which support their specialization according to the cellular ecosystem and anatomical region. In particular, ventricular cardiomyocyte subpopulations displayed an unexpected complex laminar organization across the ventricular wall and formed, with other cell subpopulations, several cellular communities. Interrogating cell-cell interactions within these communities using in vivo conditional genetic mouse models and in vitro human pluripotent stem cell systems revealed multicellular signalling pathways that orchestrate the spatial organization of cardiac cell subpopulations during ventricular wall morphogenesis. These detailed findings into the cellular social interactions and specialization of cardiac cell types constructing and remodelling the human heart offer new insights into structural heart diseases and the engineering of complex multicellular tissues for human heart repair.
Topics: Animals; Humans; Mice; Heart; Heart Diseases; Heart Ventricles; In Situ Hybridization, Fluorescence; Models, Animal; Myocardium; Myocytes, Cardiac; Single-Cell Gene Expression Analysis; Body Patterning
PubMed: 38480880
DOI: 10.1038/s41586-024-07171-z -
American Journal of Physiology. Heart... Aug 2022The complex and highly organized structural arrangement of some five billion cardiomyocytes directs the coordinated electrical activity and mechanical contraction of the... (Review)
Review
The complex and highly organized structural arrangement of some five billion cardiomyocytes directs the coordinated electrical activity and mechanical contraction of the human heart. The characteristic transmural change in cardiomyocyte orientation underlies base-to-apex shortening, circumferential shortening, and left ventricular torsion during contraction. Individual cardiomyocytes shorten ∼15% and increase in diameter ∼8%. Remarkably, however, the left ventricular wall thickens by up to 30-40%. To accommodate this, the myocardium must undergo significant structural rearrangement during contraction. At the mesoscale, collections of cardiomyocytes are organized into sheetlets, and sheetlet shear is the fundamental mechanism of rearrangement that produces wall thickening. Herein, we review the histological and physiological studies of myocardial mesostructure that have established the sheetlet shear model of wall thickening. Recent developments in tissue clearing techniques allow for imaging of whole hearts at the cellular scale, whereas magnetic resonance imaging (MRI) and computed tomography (CT) can image the myocardium at the mesoscale (100 µm to 1 mm) to resolve cardiomyocyte orientation and organization. Through histology, cardiac diffusion tensor imaging (DTI), and other modalities, mesostructural sheetlets have been confirmed in both animal and human hearts. Recent in vivo cardiac DTI methods have measured reorientation of sheetlets during the cardiac cycle. We also examine the role of pathological cardiac remodeling on sheetlet organization and reorientation, and the impact this has on ventricular function and dysfunction. We also review the unresolved mesostructural questions and challenges that may direct future work in the field.
Topics: Animals; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging; Heart Ventricles; Myocardial Contraction; Myocardium; Myocytes, Cardiac
PubMed: 35657613
DOI: 10.1152/ajpheart.00059.2022 -
Frontiers in Immunology 2023Takotsubo syndrome (TTS) is a disorder characterized by transient cardiac dysfunction with ventricular regional wall motion abnormalities, primarily thought to be caused... (Review)
Review
Takotsubo syndrome (TTS) is a disorder characterized by transient cardiac dysfunction with ventricular regional wall motion abnormalities, primarily thought to be caused by the effects of a sudden catecholamine surge on the heart. Although the majority of patients exhibit prompt recovery of their cardiac dysfunction, TTS remains associated with increased mortality rates acutely and at long-term, and there is currently no cure for TTS. Inflammation has been shown to play a key role in determining outcomes in TTS patients, as well as in the early pathogenesis of the disorder. There are also cases of TTS patients that have been successfully treated with anti-inflammatory therapies, supporting the importance of the inflammatory response in TTS. In this article, we provide a comprehensive review of the available clinical and pre-clinical literature on the immune response in TTS, in an effort to not only better understand the pathophysiology of TTS but also to generate insights on the treatment of patients with this disorder.
Topics: Humans; Takotsubo Cardiomyopathy; Heart; Catecholamines; Heart Ventricles; Inflammation
PubMed: 37868970
DOI: 10.3389/fimmu.2023.1254011 -
JACC. Cardiovascular Imaging Oct 2018Heart transplantation is an accepted treatment for select patients with end-stage heart failure. Improvements to immunosuppressive therapies and patient management have... (Review)
Review
Heart transplantation is an accepted treatment for select patients with end-stage heart failure. Improvements to immunosuppressive therapies and patient management have increased the half-life of heart transplant patients to over 10 years. Despite this success, rejection remains the "Achilles heel" of heart transplantation. The early detection of acute rejection and cardiac allograft vasculopathy are paramount to avoiding graft loss. Unlike in kidney and liver transplantation, there are no clinically validated biomarkers for detecting heart transplant rejection. Existing methods for monitoring the cardiac allograft are invasive. The endomyocardial biopsy is the standard-of-care for monitoring for acute rejection but carries risks of complications, and histologic assessment is often subjective. Equally, intracoronary angiography remains the standard-of-care for detecting cardiac allograft vasculopathy, but it is invasive and less than ideally sensitive. Newer echocardiographic techniques, computed tomography, magnetic resonance, and positron emission tomography are less invasive than conventional biopsy and show promise in excluding rejection thereby potentially decreasing the frequency of biopsies in low-risk patients. Intravascular ultrasonography and optical coherence tomography, although still invasive, improve on the assessment of the coronary tree through increased resolution, evaluation of the microvasculature, and visualization of the vessel wall. This review outlines the invasive and noninvasive imaging modalities that are employed in the routine care of heart transplant patients and examines newer techniques that are under evaluation.
Topics: Cardiac Imaging Techniques; Graft Rejection; Graft Survival; Heart; Heart Transplantation; Humans; Immunosuppressive Agents; Predictive Value of Tests; Risk Factors; Treatment Outcome
PubMed: 30286911
DOI: 10.1016/j.jcmg.2018.06.019 -
Cardiovascular Ultrasound Feb 2018Cardiac function is about creating and sustaining blood in motion. This is achieved through a proper sequence of myocardial deformation whose final goal is that of... (Review)
Review
Cardiac function is about creating and sustaining blood in motion. This is achieved through a proper sequence of myocardial deformation whose final goal is that of creating flow. Deformation imaging provided valuable contributions to understanding cardiac mechanics; more recently, several studies evidenced the existence of an intimate relationship between cardiac function and intra-ventricular fluid dynamics. This paper summarizes the recent advances in cardiac flow evaluations, highlighting its relationship with heart wall mechanics assessed through the newest techniques of deformation imaging and finally providing an opinion of the most promising clinical perspectives of this emerging field. It will be shown how fluid dynamics can integrate volumetric and deformation assessments to provide a further level of knowledge of cardiac mechanics.
Topics: Blood Flow Velocity; Cardiac Volume; Echocardiography; Heart; Heart Diseases; Hemodynamics; Humans; Hydrodynamics; Magnetic Resonance Imaging; Regional Blood Flow; Ventricular Function, Left
PubMed: 29458381
DOI: 10.1186/s12947-018-0122-2 -
Heart Failure Reviews Jul 2017The objective assessments of left ventricular (LV) and right ventricular (RV) ejection fractions (EFs) are the main important tasks of routine cardiovascular magnetic... (Review)
Review
The objective assessments of left ventricular (LV) and right ventricular (RV) ejection fractions (EFs) are the main important tasks of routine cardiovascular magnetic resonance (CMR). Over the years, CMR has emerged as the reference standard for the evaluation of biventricular morphology and function. However, changes in EF may occur in the late stages of the majority of cardiac diseases, and being a measure of global function, it has limited sensitivity for identifying regional myocardial impairment. On the other hand, current wall motion evaluation is done on a subjective basis and subjective, qualitative analysis has a substantial error rate. In an attempt to better quantify global and regional LV function; several techniques, to assess myocardial deformation, have been developed, over the past years. The aim of this review is to provide a comprehensive compendium of all the CMR techniques to assess myocardial deformation parameters as well as the application in different clinical scenarios.
Topics: Heart; Heart Diseases; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Myocardium; Stroke Volume; Ventricular Function
PubMed: 28620745
DOI: 10.1007/s10741-017-9621-8 -
International Journal For Numerical... Jan 2022Pregnancy is a unique and dynamic process characterized by significant changes in the maternal cardiovascular system that are required to satisfy the increased maternal...
Pregnancy is a unique and dynamic process characterized by significant changes in the maternal cardiovascular system that are required to satisfy the increased maternal and fetal metabolic demands. Profound structural and hemodynamic adaptations occur during healthy pregnancy that allows the mother to maintain healthy hemodynamics and provide an adequate uteroplacental blood circulation to ensure physiological fetal development. Investigating these adaptations is crucial for understanding the physiology of pregnancy and may provide important insights for the management of high-risk pregnancies. However, no previous modeling studies have investigated the maternal cardiac structural changes that occur during gestation. This study, therefore, had two aims. The first was to develop a lumped parameter model of the whole maternal circulation that is suitable for studying global hemodynamics and cardiac function at different stages of gestation. The second was to test the hypothesis that myofiber stress and wall shear stress homeostasis principles can be used to predict cardiac remodeling that occurs during normal pregnancy. Hemodynamics and cardiac variables predicted from simulations with and without controlled cardiac remodeling algorithms were compared and evaluated with reference clinical data. While both models reproduced the hemodynamic variations that arise in pregnancy, importantly, we show that the structural changes that occur with pregnancy could be predicted by assuming invariant homeostatic "target" values of myocardial wall stress and chamber wall shear stress.
Topics: Female; Heart; Heart Ventricles; Hemodynamics; Homeostasis; Humans; Pregnancy; Ventricular Remodeling
PubMed: 34599558
DOI: 10.1002/cnm.3536 -
Diagnostic and Interventional Radiology... Jan 2023A cardiac outpouching (CO) is a protrusion in a heart chamber's internal anatomical lining. Most COs are clinically insignificant, but some are of vital importance,... (Review)
Review
A cardiac outpouching (CO) is a protrusion in a heart chamber's internal anatomical lining. Most COs are clinically insignificant, but some are of vital importance, requiring immediate surgery. Cross-sectional imaging findings of COs, such as location, morphology, size, and accompanying wall motion abnormalities, play an essential role in determining the correct diagnosis and appropriate clinical management. Therefore, radiologists should be familiar with them. This article reviews the key cross-sectional imaging findings and differential diagnoses of COs.
Topics: Humans; Heart Aneurysm; Heart; Heart Ventricles
PubMed: 36960184
DOI: 10.4274/dir.2022.221419