Project description:The molecular mechanisms underlying postoperative pericardial adhesions are poorly understood. We aimed to unveil the temporal molecular and cellular mechanisms underlying tissue dynamics during adhesion formation, including inflammation, angiogenesis, and fibrosis. Using a previously established murine model, we successfully visualized the cell-based tissue dynamics during pericardial adhesion and discovered a unique angiogenic process for the induction of fibrosis. Masson’s trichrome staining revealed that collagen production was promoted from the fourth day after cardiac injury inflicted by talc injection into the pericardial cavity. A high degree of adhesion formation was observed during the stages in which collagen production was promoted. Histological analysis demonstrated that arterioles excessively sprouted from pericardial tissues in mice as well as in humans. The combination of RNA-seq and histological analyses revealed that hyperproliferative endothelial cells and myofibroblasts appeared in cytokine-exposed sprouting vessels and adhesion tissues, but not in quiescent vessels in the heart. Additionally, vascular smooth muscle cells were dedifferentiated from the contractile to the synthetic phenotype in heart tissue, and matrix metalloproteinase-dependent tissue remodeling in the pre-angiogenic stage potentially contributed to neovascularization and fibrosis in the pericardial cavity. Our findings will assist in developing prevention strategies for pericardial adhesions by targeting the recruitment of vascular cells from heart tissues.
Project description:Pericardial sac surrounding the heart contains pericardial fluid (PF), which is rich in exosomes. PF exosomes increase angiogenesis in hypoxic endothelial cells and in animal model of hindlimb ischemia by passing the proangiogenic miRNAs to recipient cells. However, under pathological conditions such as diabetes, exosome cargo composition changes and harmful miRNAs can be transferred to the recipient cells and induce more deleterious effects in target tissues. In order to check cargo composition of different PF exosomes, we used PF exosomes from non-diabetic aortic valve replacement (AVR), mitral valve replacement (MVR), coronary artery bypass grafting (CABG) patients and CABG patients with diabetes.
Project description:we examined 24 pericardial effusion patients and obtained pericardial fluid. To identify novel biomarker for detection cancer, detected transcriptome-based molecualr signature of compare pathologic cancer patients and non-cancer patients.
Project description:To better characterize the role of whole pericardial adipose tissue (PCAT) in the pathogenesis of disease, we performed a large-scale unbiased analysis of the transcriptional differences between pericardial and subcutaneous adipose tissue, analysing 53 microarrays across 19 individuals.
Project description:To better characterize the role of PCAT in the pathogenesis of disease, we performed a large-scale unbiased analysis of the transcriptional differences between pericardial and subcutaneous adipose tissue, analysing 53 microarrays across 19 individuals. Patients who underwent elective coronary artery bypass grafting and/or cardiac valve replacement surgeries participated in the study. Pericardial adipose tissue and subcutaneous adipose tissue were harvested from patients.
Project description:We used single cell RNA-seq to comprehensively map all retinal microglia populations in a mouse model of oxygen-induced PR. We unveiled several unique types of PR-associated microglia (PRAM) and identified markers, signaling pathways, and regulons associated with these cells. Among these microglial subpopulations, we found a highly proliferative subset of cells with a high self-renewal capacity and a subset of cells with hypermetabolism that expresses high levels of activating microglia markers, glycolytic enzymes, and pro-angiogenic insulin-like growth factor 1. Immunohistochemical staining shows that PRAMs were spatially located within neovascular tufts. These unique microglial subtypes have the potential to promote retinal angiogenesis, which may have important implications for the future treatment of PR and other ocular diseases characterized by pathological angiogenesis.
Project description:The pericardial fluid (PF) surrounds the heart and it is contained in the pericardial sac. PF contains myocardial-derived factors. MicroRNAs (miRNAs) are negative post-transcriptional regulators of their target genes and they can be released into extracellular vesicles (EVs) contributing to cell-to-cell communication. We hypothesize that the PF contains miRNAs of myocardial origin and that represents a niche for the exchange of miRNAs between heart cells. In order to investigate whether PF contains functionally active miRNAs, miRNA expression profiles on PF samples collected from three patients undergoing aortic valve replacement (AVR) surgery performed during cardiopulmonary-bypass (CPB), were genereted.
Project description:Pericardial fluid is enriched by biologically active molecules of cardiovascular origin including microRNAs. Investigation of the disease-specific extracellular microRNAs could shed light on the molecular processes underlying disease development. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart disease characterized by life-threatening arrhythmias and progressive heart failure development. The current data about the association between microRNAs and ARVC development are limited. We performed small RNA sequence analysis of microRNAs of pericardial fluid samples obtained during transcutaneous epicardial access for ventricular tachycardia (VT) ablation of six patients with definite ARVC and three post-infarction VT patients. Disease-associated microRNAs of pericardial fluid were identified. Enrichment analysis of differentially expressed microRNAs revealed their close linkage to cardiac diseases.