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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 -
Heart Asia 2018A 32-year-old woman with no other medical history presented with 1-month history of fever, weight loss and dyspnoea. On examination she had elevated jugular venous...
CASE PRESENTATION
A 32-year-old woman with no other medical history presented with 1-month history of fever, weight loss and dyspnoea. On examination she had elevated jugular venous pressure and tachycardia. Her chest X-ray posterioranterior view (figure 1A) showed a rounded mass in the right cardiophrenic angle obscuring the right atrial margin, producing a 'silhouette' sign. Echocardiography showed a large cystic mass with thickened pericardium, lateral to the right atrium, causing right atrial compression (figure 1B). CT image of the chest showed a cystic lesion compressing the right atrium with thickened pericardium (figure 2A). There were no other lesions found in the lungs or other organs. Laboratory tests showed elevated erythrocyte sedimentation rate (ESR: 96 mm/hour) and C reactive protein (CRP: 32 mg/L). Excision of the mass with partial pericardiectomy was done. Intraoperatively, there was a cyst with thickened pericardial wall and thick yellowish brown fluid. Histopathology of the tissue is shown in figure 2B.Figure 1(A) Chest X-ray posterioranterior view showing a rounded mass in the right cardiophrenic angle. (B) Transthoracic echocardiography apical four-chamber view showing the cystic mass.Figure 2(A) CT of the chest sagittal view showing cystic lesion compressing the right atrium with thickened pericardium. (B) Histopathology specimen of the pericardial tissue.
QUESTION
What is the diagnosis and what should be the management strategy?Congenital pericardial cyst and no further evaluation required.Features are suggestive of tuberculous pericardial cyst and needs treatment with antituberculosis regimen.Features suggestive of pericardial hydatid cyst and requires treatment with albendazole.Features are suggestive of viral pericarditis with encysted effusion.
PubMed: 30116306
DOI: 10.1136/heartasia-2018-011071 -
Cell Reports Mar 2020Cardiac ischemia leads to the loss of myocardial tissue and the activation of a repair process that culminates in the formation of a scar whose structural...
Cardiac ischemia leads to the loss of myocardial tissue and the activation of a repair process that culminates in the formation of a scar whose structural characteristics dictate propensity to favorable healing or detrimental cardiac wall rupture. To elucidate the cellular processes underlying scar formation, here we perform unbiased single-cell mRNA sequencing of interstitial cells isolated from infarcted mouse hearts carrying a genetic tracer that labels epicardial-derived cells. Sixteen interstitial cell clusters are revealed, five of which were of epicardial origin. Focusing on stromal cells, we define 11 sub-clusters, including diverse cell states of epicardial- and endocardial-derived fibroblasts. Comparing transcript profiles from post-infarction hearts in C57BL/6J and 129S1/SvImJ inbred mice, which displays a marked divergence in the frequency of cardiac rupture, uncovers an early increase in activated myofibroblasts, enhanced collagen deposition, and persistent acute phase response in 129S1/SvImJ mouse hearts, defining a crucial time window of pathological remodeling that predicts disease outcome.
Topics: Animals; Cicatrix; Homeostasis; Mice; Mice, Inbred Strains; Myocardial Infarction; Myocardium; Myofibroblasts; Pericardium; Phenotype; RNA-Seq; Rupture; Single-Cell Analysis; Stromal Cells
PubMed: 32130914
DOI: 10.1016/j.celrep.2020.02.008 -
Nature Biotechnology Dec 2023The epicardium, the mesothelial envelope of the vertebrate heart, is the source of multiple cardiac cell lineages during embryonic development and provides signals that...
The epicardium, the mesothelial envelope of the vertebrate heart, is the source of multiple cardiac cell lineages during embryonic development and provides signals that are essential to myocardial growth and repair. Here we generate self-organizing human pluripotent stem cell-derived epicardioids that display retinoic acid-dependent morphological, molecular and functional patterning of the epicardium and myocardium typical of the left ventricular wall. By combining lineage tracing, single-cell transcriptomics and chromatin accessibility profiling, we describe the specification and differentiation process of different cell lineages in epicardioids and draw comparisons to human fetal development at the transcriptional and morphological levels. We then use epicardioids to investigate the functional cross-talk between cardiac cell types, gaining new insights into the role of IGF2/IGF1R and NRP2 signaling in human cardiogenesis. Finally, we show that epicardioids mimic the multicellular pathogenesis of congenital or stress-induced hypertrophy and fibrotic remodeling. As such, epicardioids offer a unique testing ground of epicardial activity in heart development, disease and regeneration.
Topics: Humans; Pericardium; Heart; Myocardium; Cell Differentiation; Cell Lineage; Biology
PubMed: 37012447
DOI: 10.1038/s41587-023-01718-7 -
Journal of Clinical Medicine May 2021Mesothelioma is an aggressive disease arising from parietal pleura. Surgery is a valuable option in the frame of a multimodality treatment. Several surgical approaches... (Review)
Review
Mesothelioma is an aggressive disease arising from parietal pleura. Surgery is a valuable option in the frame of a multimodality treatment. Several surgical approaches have been standardized with the aim of a macroscopic complete resection; these often require homolateral diaphragm and pericardial resection and reconstruction. Extrapleural pneumonectomy (EPP) and extended pleurectomy decortication (EPD) have been recognized as radical surgical procedures. Nevertheless, both operations are technically challenging and associated with a significant rate of peri-operative morbidity and non-negligible mortality. The diaphragmatic and pericardial reconstruction technique is mandatory to avoid respiratory impairment and to reduce post-operative complications like gastric and cardiac herniation. Moreover, in the case of localized chest wall recurrence, surgery might be considered a valuable therapeutical option for highly selected and fit patients. All the technical aspects of the resection and reconstruction of the diaphragm, pericardium, and chest wall are described as well as the possible use of new minimally invasive techniques. In addition, the choice of different prosthetic materials, considering the most recent innovations in the field, are discussed.
PubMed: 34073544
DOI: 10.3390/jcm10112330 -
Journal of the American College of... Oct 2022Studies with short-term follow-up have demonstrated favorable effects of weight loss (WL) on the heart, but little information is available regarding long-term effects... (Observational Study)
Observational Study
BACKGROUND
Studies with short-term follow-up have demonstrated favorable effects of weight loss (WL) on the heart, but little information is available regarding long-term effects or effects of visceral fat reduction.
OBJECTIVES
The purpose of this study was to evaluate the effects of long-term WL following bariatric surgery on cardiac structure, function, ventricular interaction, and body composition, including epicardial adipose thickness and abdominal visceral adipose tissue (VAT).
METHODS
A total of 213 obese patients underwent echocardiography before and >180 days following bariatric surgery. Abdominal VAT area was measured by computed tomography in 52 of these patients.
RESULTS
After 5.3 years (IQR: 2.9-7.9 years), body mass index (BMI) decreased by 22%, with favorable reductions in blood pressure, fasting glucose, and left ventricular (LV) remodeling in the full sample. In the subgroup of patients with abdominal computed tomography, VAT area decreased by 30%. In all subjects, epicardial adipose thickness was reduced by 14% (both P < 0.0001) in tandem with reductions in ventricular interdependence. LV and right ventricular longitudinal strain improved following WL, but left atrial (LA) strain deteriorated, while LA volume and estimated LA pressures increased. In subgroup analysis, LV wall thickness and strain correlated more strongly with VAT than BMI at baseline, and reductions in LV mass following surgery were correlated with decreases in VAT, but not BMI.
CONCLUSIONS
In this observational study, weight loss following bariatric surgery was associated with epicardial fat reduction, reduced ventricular interaction, LV reverse remodeling, and improved longitudinal biventricular mechanics, but LA myopathy and hemodynamic congestion still progressed. Reduction in visceral fat was associated with favorable cardiac effects, suggesting this might be a key target of WL interventions.
Topics: Bariatric Surgery; Glucose; Heart Ventricles; Humans; Pericardium; Ventricular Function, Left; Ventricular Remodeling; Weight Loss
PubMed: 36229085
DOI: 10.1016/j.jacc.2022.08.738 -
The British Journal of Radiology Sep 2020Epicardial adipose tissue (EAT) is a metabolically activated beige adipose tissue, non-homogeneously surrounding the myocardium. Physiologically, EAT regulates toxic... (Review)
Review
Epicardial adipose tissue (EAT) is a metabolically activated beige adipose tissue, non-homogeneously surrounding the myocardium. Physiologically, EAT regulates toxic fatty acids, protects the coronary arteries against mechanical strain, regulates proinflammatory cytokines, stimulates the production of nitric oxide, reduces oxidative stress, and works as a thermogenic source against hypothermia. Conversely, EAT has pathologic paracrine interactions with the surrounded vessels, and might favour the onset of atrial fibrillation. In addition, initial atherosclerotic lesions can promote inflammation and trigger the EAT production of cytokines increasing vascular inflammation, which, in turn, may help the development of collateral vessels but also of self-stimulating, dysregulated inflammatory process, increasing coronary artery disease severity. Variations in EAT were also linked to metabolic syndrome. Echocardiography first estimated EAT measuring its thickness on the free wall of the right ventricle but does not allow accurate volumetric EAT estimates. Cardiac CT (CCT) and cardiac MR (CMR) allow for three-dimensional EAT estimates, the former showing higher spatial resolution and reproducibility but being limited by radiation exposure and long segmentation times, the latter being radiation-free but limited by lower spatial resolution and reproducibility, higher cost, and difficulties for obese patients. EAT radiodensity at CCT could to be related to underlying metabolic processes. The correlation between EAT and response to certain pharmacological therapies has also been investigated, showing promising results. In the future, semi-automatic or fully automatic techniques, machine/deep-learning methods, if validated, will facilitate research for various EAT measures and may find a place in CCT/CMR reporting.
Topics: Adipose Tissue, Beige; Biomarkers; Coronary Artery Disease; Coronary Vessels; Cytokines; Echocardiography; Heart; Humans; Magnetic Resonance Imaging; Myocardium; Pericardium; Reproducibility of Results; Tomography, X-Ray Computed
PubMed: 31782934
DOI: 10.1259/bjr.20190770