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Future Cardiology Jan 2012The mammalian heart loses its regenerative capacity during early postnatal stages; consequently, individuals surviving myocardial infarction are at risk of heart failure... (Review)
Review
The mammalian heart loses its regenerative capacity during early postnatal stages; consequently, individuals surviving myocardial infarction are at risk of heart failure due to excessive fibrosis and maladaptive remodeling. There is an urgent need, therefore, to develop novel therapies for myocardial and coronary vascular regeneration. The epicardium-derived cells present a tractable resident progenitor source with the potential to stimulate neovasculogenesis and contribute de novo cardiomyocytes. The ability to revive ordinarily dormant epicardium-derived cells lies in the identification of key stimulatory factors, such as Tβ4, and elucidation of the molecular cues used in the embryo to orchestrate cardiovascular development. myocardial infarction injury signaling reactivates the adult epicardium; understanding the timing and magnitude of these signals will enlighten strategies for myocardial repair.
Topics: Coronary Vessels; Extracellular Matrix; Humans; Myocardial Infarction; Myocardium; Myocytes, Cardiac; Pericardium; Regenerative Medicine; Signal Transduction; Stem Cells; Thymosin; Vascular Endothelial Growth Factor A
PubMed: 22185446
DOI: 10.2217/fca.11.87 -
TheScientificWorldJournal Nov 2007During heart development, cells of the primary and secondary heart field give rise to the myocardial component of the heart. The neural crest and epicardium provide the... (Review)
Review
During heart development, cells of the primary and secondary heart field give rise to the myocardial component of the heart. The neural crest and epicardium provide the heart with a considerable amount of nonmyocardial cells that are indispensable for correct heart development. During the past 2 decades, the importance of epicardium-derived cells (EPDCs) in heart formation became increasingly clear. The epicardium is embryologically formed by the outgrowth of proepicardial cells over the naked heart tube. Following epithelial-mesenchymal transformation, EPDCs form the subepicardial mesenchyme and subsequently migrate into the myocardium, and differentiate into smooth muscle cells and fibroblasts. They contribute to the media of the coronary arteries, to the atrioventricular valves, and the fibrous heart skeleton. Furthermore, they are important for the myocardial architecture of the ventricular walls and for the induction of Purkinje fiber formation. Whereas the exact signaling cascades in EPDC migration and function still need to be elucidated, recent research has revealed several factors that are involved in EPDC migration and specialization, and in the cross-talk between EPDCs and other cells during heart development. Among these factors are the Ets transcription factors Ets-1 and Ets-2. New data obtained with lentiviral antisense constructs targeting Ets-1 and Ets-2 specifically in the epicardium indicate that both factors are independently involved in the migratory behavior of EPDCs. Ets-2 seems to be especially important for the migration of EPDCs into the myocardial wall, and to subendocardial positions in the atrioventricular cushions and the trabeculae. With respect to the clinical importance of correct EPDC development, the relation with coronary arteriogenesis has been noted well before. In this review, we also propose a role for EPDCs in cardiac looping, and emphasize their contribution to the development of the valves and myocardial architecture. Lastly, we focus on the congenital heart anomalies that might be caused primarily by an epicardial developmental defect.
Topics: Animals; Heart Defects, Congenital; Humans; Morphogenesis; Myocytes, Cardiac; Pericardium; Proto-Oncogene Protein c-ets-1; Proto-Oncogene Protein c-ets-2
PubMed: 18040540
DOI: 10.1100/tsw.2007.294 -
JACC. Cardiovascular Imaging Jun 2020Frequently, multimodality imaging is indispensable in the care of patients with pericardial disease. With cardiac magnetic resonance imaging, pericardial inflammation... (Review)
Review
Frequently, multimodality imaging is indispensable in the care of patients with pericardial disease. With cardiac magnetic resonance imaging, pericardial inflammation can be characterized as acute, subacute, or chronic. This spectrum of inflammation is variably associated with reduced compliance of the pericardium, which may result in constrictive pathophysiology, typically well-defined with echocardiography. This interplay between inflammation and hemodynamics is often optimally characterized with multimodality imaging and has redefined the approach of pericardiologists to diagnose, prognosticate, and tailor individual therapies.
Topics: Acute Disease; Asymptomatic Diseases; Cardiac Imaging Techniques; Chronic Disease; Clinical Decision-Making; Hemodynamics; Humans; Multimodal Imaging; Pericarditis; Pericardium; Predictive Value of Tests
PubMed: 31734199
DOI: 10.1016/j.jcmg.2019.08.027 -
Stem Cell Reports Jul 2023The epicardium plays an essential role in cardiogenesis by providing cardiac cell types and paracrine cues to the developing myocardium. The human adult epicardium is...
The epicardium plays an essential role in cardiogenesis by providing cardiac cell types and paracrine cues to the developing myocardium. The human adult epicardium is quiescent, but recapitulation of developmental features may contribute to adult cardiac repair. The cell fate of epicardial cells is proposed to be determined by the developmental persistence of specific subpopulations. Reports on this epicardial heterogeneity have been inconsistent, and data regarding the human developing epicardium are scarce. Here we specifically isolated human fetal epicardium and used single-cell RNA sequencing to define its composition and to identify regulators of developmental processes. Few specific subpopulations were observed, but a clear distinction between epithelial and mesenchymal cells was present, resulting in novel population-specific markers. Additionally, we identified CRIP1 as a previously unknown regulator involved in epicardial epithelial-to-mesenchymal transition. Overall, our human fetal epicardial cell-enriched dataset provides an excellent platform to study the developing epicardium in great detail.
Topics: Adult; Humans; Pericardium; Myocardium; Epithelial-Mesenchymal Transition; Fetus; Single-Cell Analysis; Carrier Proteins; LIM Domain Proteins
PubMed: 37390825
DOI: 10.1016/j.stemcr.2023.06.002 -
Folia Histochemica Et Cytobiologica 2016Normal pericardium consists of an outer sac called fibrous pericardium and an inner one called serous pericardium. The two layers of serous pericardium: visceral and... (Review)
Review
Normal pericardium consists of an outer sac called fibrous pericardium and an inner one called serous pericardium. The two layers of serous pericardium: visceral and parietal are separated by the pericardial cavity, which contains 20 to 60 mL of the plasma ultrafiltrate. The pericardium acts as mechanical protection for the heart and big vessels, and a lubrication to reduce friction between the heart and the surrounding structures. A very important role in all aspects of pericardial functions is played by mesothelial cells. The mesothelial cells form a monolayer lining the serosal cavity and play an important role in antigen presentation, inflammation and tissue repair, coagulation and fibrinolysis. The two major types of mesothelial cells, flat or cuboid, differ substantially in their ultrastructure and, probably, functions. The latter display abundant microvilli, RER, Golgi dense bodies, membrane-bound vesicles and intracellular vacuoles containing electron-dense material described as dense bodies. The normal structure and functions of the pericardium determine correct healing after its injury as a result of surgery or microbial infection. The unfavorable resolution of acute or chronic pericarditis leads to the formation of adhesions between pericardial leaflets which may lead to serious complications.
Topics: Animals; Heart; Humans; Pericardium
PubMed: 27654013
DOI: 10.5603/FHC.a2016.0014 -
Journal of Cellular and Molecular... May 2010Reactivation of endogenous epicardium after ischemia The proepicardial-derived epicardium covers the myocardium and after a process of epithelial-mesenchymal transition... (Review)
Review
Reactivation of endogenous epicardium after ischemia The proepicardial-derived epicardium covers the myocardium and after a process of epithelial-mesenchymal transition (EMT) forms epicardium-derived cells (EPDCs). These cells migrate into the myocardium and show an essential role in the induction of the ventricular compact myocardium and the differentiation of the Purkinje fibres. EPDCs are furthermore the source of the interstitial fibroblast, the coronary smooth muscle cell and the adventitial fibroblast. The possible differentiation into cardiomyocytes, endothelial cells and the recently described telocyte and other cells in the cardiac stem cell niche needs further investigation. Surgically or genetically disturbed epicardial and EPDC differentiation leads to a spectrum of abnormalities varying from thin undifferentiated myocardium, which can be embryonic lethal, to a diminished coronary vascular bed with even absent main coronary arteries. The embryonic potential of EPDCs has been translated to both structural and functional congenital malformations and adult cardiac disease, like development of Ebstein's malformation, arrhythmia and cardiomyopathies. Furthermore, the use of adult EPDCs as a stem cell source has been explored, showing in an animal model of myocardial ischemia the recapitulation of the embryonic program with improved function, angiogenesis and less adverse remodeling. Combining EPDCs and adult cardiomyocyte progenitor cells synergistically improved these results. The contribution of injected EPDCs was instructive rather than constructive. The finding of reactivation of the endogenous epicardium in ischemia with re-expression of developmental genes and renewed EMT marks the onset of a novel therapeutic focus.
Topics: Adult Stem Cells; Cardiovascular Diseases; Epithelium; Humans; Myocardial Ischemia; Pericardium; Wound Healing
PubMed: 20646126
DOI: 10.1111/j.1582-4934.2010.01077.x -
Wound Repair and Regeneration :... 2012Cardiovascular disease is the leading cause of death in the U.S. and worldwide. Failure to properly repair or regenerate damaged cardiac tissues after myocardial... (Review)
Review
Cardiovascular disease is the leading cause of death in the U.S. and worldwide. Failure to properly repair or regenerate damaged cardiac tissues after myocardial infarction is a major cause of heart failure. In contrast to humans and other mammals, zebrafish hearts regenerate after substantial injury or tissue damage. Here, we review recent progress in studying zebrafish heart regeneration, addressing the molecular and cellular responses in the three tissue layers of the heart: myocardium, epicardium, and endocardium. We also compare different injury models utilized to study zebrafish heart regeneration and discuss the differences in responses to injury between mammalian and zebrafish hearts. By learning how zebrafish hearts regenerate naturally, we can better design therapeutic strategies for repairing human hearts after myocardial infarction.
Topics: Animals; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Cell Proliferation; Endocardium; Heart; Humans; Models, Animal; Myocardium; Myocytes, Cardiac; Pericardium; Regeneration; Zebrafish
PubMed: 22818295
DOI: 10.1111/j.1524-475X.2012.00814.x -
Circulation Research May 2020Fibro-fatty infiltration of subepicardial layers of the atrial wall has been shown to contribute to the substrate of atrial fibrillation.
RATIONALE
Fibro-fatty infiltration of subepicardial layers of the atrial wall has been shown to contribute to the substrate of atrial fibrillation.
OBJECTIVE
Here, we examined if the epicardium that contains multipotent cells is involved in this remodeling process.
METHODS AND RESULTS
One hundred nine human surgical right atrial specimens were evaluated. There was a relatively greater extent of epicardial thickening and dense fibro-fatty infiltrates in atrial tissue sections from patients aged over 70 years who had mitral valve disease or atrial fibrillation when compared with patients aged less than 70 years with ischemic cardiomyopathy as indicated using logistic regression adjusted for age and gender. Cells coexpressing markers of epicardial progenitors and fibroblasts were detected in fibro-fatty infiltrates. Such epicardial remodeling was reproduced in an experimental model of atrial cardiomyopathy in rat and in Wilms tumor 1 (WT1);ROSA-tdT mice. In the latter, genetic lineage tracing demonstrated the epicardial origin of fibroblasts within fibro-fatty infiltrates. A subpopulation of human adult epicardial-derived cells expressing PDGFR (platelet-derived growth factor receptor)-α were isolated and differentiated into myofibroblasts in the presence of Ang II (angiotensin II). Furthermore, single-cell RNA-sequencing analysis identified several clusters of adult epicardial-derived cells and revealed their specification from adipogenic to fibrogenic cells in the rat model of atrial cardiomyopathy.
CONCLUSIONS
Epicardium is reactivated during the formation of the atrial cardiomyopathy. Subsets of adult epicardial-derived cells, preprogrammed towards a specific cell fate, contribute to fibro-fatty infiltration of subepicardium of diseased atria. Our study reveals the biological basis for chronic atrial myocardial remodeling that paves the way of atrial fibrillation.
Topics: Action Potentials; Adipocytes; Adipose Tissue; Aged; Animals; Atrial Fibrillation; Atrial Remodeling; Cardiomyopathies; Cell Lineage; Disease Models, Animal; Female; Fibroblasts; Fibrosis; Heart Atria; Heart Rate; Humans; Male; Mice, Inbred C57BL; Mice, Transgenic; Myocardium; Pericardium; Rats, Wistar; Stem Cells; WT1 Proteins
PubMed: 32175811
DOI: 10.1161/CIRCRESAHA.119.316251 -
Methodist DeBakey Cardiovascular Journal Apr 2013
Topics: Adult; Drug Administration Schedule; Echocardiography, Doppler; Female; Glucocorticoids; Humans; Magnetic Resonance Imaging; Multimodal Imaging; Pericarditis, Constrictive; Pericardium; Prednisone; Remission Induction; Time Factors; Treatment Outcome
PubMed: 23805352
DOI: 10.14797/mdcj-9-2-118 -
Developmental Cell Mar 2020The epicardium is essential during cardiac development, homeostasis, and repair, and yet fundamental insights into its underlying cell biology, notably epicardium...
The epicardium is essential during cardiac development, homeostasis, and repair, and yet fundamental insights into its underlying cell biology, notably epicardium formation, lineage heterogeneity, and functional cross-talk with other cell types in the heart, are currently lacking. In this study, we investigated epicardial heterogeneity and the functional diversity of discrete epicardial subpopulations in the developing zebrafish heart. Single-cell RNA sequencing uncovered three epicardial subpopulations with specific genetic programs and distinctive spatial distribution. Perturbation of unique gene signatures uncovered specific functions associated with each subpopulation and established epicardial roles in cell adhesion, migration, and chemotaxis as a mechanism for recruitment of leukocytes into the heart. Understanding which mechanisms epicardial cells employ to establish a functional epicardium and how they communicate with other cardiovascular cell types during development will bring us closer to repairing cellular relationships that are disrupted during cardiovascular disease.
Topics: Animals; Cell Lineage; Gene Expression Regulation, Developmental; Pericardium; RNA-Seq; Single-Cell Analysis; Transcriptome; Zebrafish
PubMed: 32084358
DOI: 10.1016/j.devcel.2020.01.023