Fibrotic Remodelling of Epicardial Adipose Tissue in Patients with Atrial Fibrillation: Comparative Analyses of Histological Findings and Computed Tomographic Imaging
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PROVIDER: PRJNA646255 | ENA |
REPOSITORIES: ENA
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Project description:Aims: We tested the hypothesis that central-marginal dispersion in adipocyte diameter in epicardial adipose tissue (EAT) would represent fibrotic remodelling of EAT, a crucial state to promote atrial myocardial fibrosis to form a substrate of atrial fibrillation (AF). We also investigated whether the central-marginal EAT density ratio by the analyses of computed tomographic (CT) imaging could predict the central-marginal adipocyte diameter ratio in EAT. Methods and results: Left atrial appendage samples were obtained from 76 consecutive AF patients during cardiovascular surgery. EAT at central area (Central EAT) and that adjacent to atrial myocardium (Marginal EAT) were evaluated. Compared to the Central EAT, the dimeter of adipocytes was smaller, fibrotic remodeling of EAT (EAT fibrosis) was more severe, and the infiltration of CD3-, CD68-, or α-SMA-positive cells were more abundant in the Marginal EAT. EAT fibrosis positively correlated with adipocyte diameter in the Central EAT, while it negatively correlated with that in the Marginal EAT, resulting in the tightly positive correlation between EAT fibrosis and the ratio of central to marginal adipocyte diameter (C/M diameter ratio) (r=0.73, p<0.01). The C/M diameter ratio was greater in patients with persistent AF (PeAF) than in those with paroxysmal AF (PAF) (p<0.01). The CT density in Central EAT and Marginal EAT was measured and their ratio (C/M density ratio) was calculated. The C/M density ratio correlated tightly with the C/M diameter ratio (r=0.69, p<0.01). Conclusion: Our results suggest that C/M adipocyte diameter ratio was associated with fibrotic remodeling of EAT and progression of AF. Our results also suggest that C/M adipocyte diameter ratio could be accurately predicted by the analyses of CT findings noninvasively.
2021-08-25 | GSE154436 | GEO
Project description:Identification of epicardium-enriched genes in the embryonic heart. The epicardium encapsulates the heart and functions as a source of multipotent progenitor cells and paracrine factors essential for cardiac development and repair. Injury of the adult heart results in re-activation of a developmental gene program in the epicardium, but the transcriptional basis of epicardial gene expression has not been delineated. We established a mouse embryonic heart organ culture and gene expression system that facilitated the identification of epicardial enhancers activated during heart development and injury. Epicardial activation of these enhancers depends on a combinatorial transcriptional code centered on CCAAT/enhancer binding protein (C/EBP) transcription factors. Disruption of C/EBP signaling in the adult epicardium reduced injury-induced neutrophil infiltration and improved cardiac function. These findings reveal a transcriptional basis for epicardial activation and heart injury, providing a platform for enhancing cardiac regeneration. Total RNA obtained from lacZ-positive epicardial cells isolated from the E11.5 Tcf21lacZ hearts compared to total dissociated heart cells
2012-11-01 | E-GEOD-41959 | biostudies-arrayexpress
Project description:Accumulating studies have suggested that epicardial adipose tissue play an important role in the pathogenesis of atrial fibrillation (AF), but few have characterized the underlying mechanism between their interactions. Recent evidence suggested that bioactive molecules secreted from EAT, including exosomes carrying non-coding RNAs, may modulate atrial remodeling. The aim of the present study was to investigate the expression profile of mRNAs and ncRNAs in EAT with AF.
2019-08-07 | GSE135445 | GEO
Project description:BackgroundFibrotic remodeling of epicardial adipose tissue (EAT) is crucial for proinflammatory atrial myocardial fibrosis, which leads to atrial fibrillation (AF).ObjectivesWe tested the hypothesis that the ratio of central to marginal adipocyte diameter in EAT represents its fibrotic remodeling. Based on a similar concept, we also tested whether the percent (%) change in EAT fat attenuation determined using computed tomographic (CT) images can detect this remodeling.MethodsLeft atrial appendages were obtained from 76 consecutive AF patients during cardiovascular surgery. EAT in the central area (central EAT: C-EAT) and that adjacent to the atrial myocardium (Marginal EAT: M-EAT) were evaluated histologically. CT images for all of the 76 patients were also analyzed.ResultsThe adipocyte diameter was smaller, fibrotic remodeling of EAT (EAT fibrosis) was more severe, and infiltration of macrophages and myofibroblasts was more extensive in M-EAT than in C-EAT. EAT fibrosis was positively correlated with adipocyte diameter in C-EAT and negatively correlated in M-EAT, resulting in a positive correlation between EAT fibrosis and the ratio of central to marginal adipocyte diameter (C/M diameter ratio; r = 0.73, P < .01). The C/M diameter ratio was greater in patients with persistent AF than in those with paroxysmal AF. CT images demonstrated that the %change in EAT fat attenuation was positively correlated with EAT fibrosis.ConclusionOur results suggest that the central-to-marginal adipocyte diameter ratio is tightly associated with fibrotic remodeling of EAT. In addition, the %change in EAT fat attenuation determined using CT imaging can detect remodeling noninvasively.
| S-EPMC8369308 | biostudies-literature
Project description:Nonmuscle myosin IIB (NMIIB; heavy chain encoded by MYH10) is essential for cardiac myocyte cytokinesis. The role of NMIIB in other cardiac cells is not known. Here, we show that NMIIB is required in epicardial formation and functions to support myocardial proliferation and coronary vessel development. Ablation of NMIIB in epicardial cells results in disruption of epicardial integrity with a loss of E-cadherin at cell-cell junctions and a focal detachment of epicardial cells from the myocardium. NMIIB-knockout and blebbistatin-treated epicardial explants demonstrate impaired mesenchymal cell maturation during epicardial epithelial-mesenchymal transition. This is manifested by an impaired invasion of collagen gels by the epicardium-derived mesenchymal cells and the reorganization of the cytoskeletal structure. Although there is a marked decrease in the expression of mesenchymal genes, there is no change in Snail (also known as Snai1) or E-cadherin expression. Studies from epicardium-specific NMIIB-knockout mice confirm the importance of NMIIB for epicardial integrity and epicardial functions in promoting cardiac myocyte proliferation and coronary vessel formation during heart development. Our findings provide a novel mechanism linking epicardial formation and epicardial function to the activity of the cytoplasmic motor protein NMIIB.
2017-07-21 | GSE101701 | GEO
Project description:Background and aimsThis study aimed to histologically validate atrial structural remodelling associated with atrial fibrillation.Methods and resultsPatients undergoing atrial fibrillation ablation and endomyocardial atrial biopsy were included (n = 230; 67 ± 12 years old; 69 women). Electroanatomic mapping was performed during right atrial pacing. Voltage at the biopsy site (Vbiopsy), global left atrial voltage (VGLA), and the proportion of points with fractionated electrograms defined as ≥5 deflections in each electrogram (%Fractionated EGM) were evaluated. SCZtotal was calculated as the total width of slow conduction zones, defined as regions with a conduction velocity of <30 cm/s. Histological factors potentially associated with electroanatomic characteristics were evaluated using multiple linear regression analyses. Ultrastructural features and immune cell infiltration were evaluated by electron microscopy and immunohistochemical staining in 33 and 60 patients, respectively. Fibrosis, intercellular space, myofibrillar loss, and myocardial nuclear density were significantly associated with Vbiopsy (P = .014, P < .001, P < .001, and P = .002, respectively) and VGLA (P = .010, P < .001, P = .001, and P < .001, respectively). The intercellular space was associated with the %Fractionated EGM (P = .001). Fibrosis, intercellular space, and myofibrillar loss were associated with SCZtotal (P = .028, P < .001, and P = .015, respectively). Electron microscopy confirmed plasma components and immature collagen fibrils in the increased intercellular space and myofilament lysis in cardiomyocytes, depending on myofibrillar loss. Among the histological factors, the severity of myofibrillar loss was associated with an increase in macrophage infiltration.ConclusionHistological correlates of atrial structural remodelling were fibrosis, increased intercellular space, myofibrillar loss, and decreased nuclear density. Each histological component was defined using electron microscopy and immunohistochemistry studies.
| S-EPMC10499545 | biostudies-literature
Project description:The epicardium is a mesothelial layer covering the myocardium and contributes to different cardiac lineage descendants during cardiogenesis. Fine-tuned balanced signaling defines epicardial specification and regulates cell plasticity and cell-fate decisions of epicardial-derived cells (EPCDs) by epicardial-to-mesenchymal transition (EMT). However, powerful tools to investigate epicardial cell function, including markers with pivotal roles in developmental signaling, are still lacking. Here, we recapitulated embryonic epicardiogenesis using human induced pluripotent stem cells (hiPSCs) and identified type II classical cadherin CDH18 as a novel biomarker defining lineage specification in human developing epicardium. The loss of CDH18 led to the onset of EMT and specific differentiation towards cardiac smooth muscle cells. Furthermore, GATA4 regulated epicardial CDH18 expression. These results demonstrate the production and enrichment of hiPSC-derived epicardial cells via the tracing of CDH18 expression, providing a model for investigating epicardial function in human development and disease and enabling new possibilities for regenerative medicine.
2022-02-18 | GSE165450 | GEO
Project description:Single cell RNA sequencing (scRNA-Seq) is applied to charaterize the pro-epicardial cells (proEpiCs) in mouse pro-epicardial organ (PEO).
2020-04-04 | GSE148040 | GEO
Project description:Atrial fibrillation (AF) is the most common sustained arrythmia, but the potential molecular indicators involved in structural and electronical remodeling remains to be clarified. Epicardial adipose tissue (EAT), a visceral fat depot surrounding the heart, is increasingly recognized to be metabolically active and has been proposed with an arrthymogenicity nature. It is able to secret a myriad of bioactive molecules, including exosomes carrying tRNA derived small RNAs (tsRNAs). Accumulating findings have suggested that these specific tsRNAs dynamically impact fundamental cellular processes, but there are no studies discovering the association between tsRNAs of EAT and AF, and their interactions and potential signaling pathways remain to be elucidated.
2022-08-11 | GSE210705 | GEO
Project description:The goal of the present study is to determine the miRNA cargo present in epicardial extracellular vesicles. For that, epicardial cells and human primary epicardial cells were cultured. Conditioned media was isolated from mouse epicardial cells and human primary epicardial cells derived from right atrial appendages in two different states: “cobble” (inactive) cells and “spindle” (active) . RNA from EVs was isolated and sequenced to determine the miRNA content profile.
2020-11-18 | GSE161630 | GEO