Human ischemic cardiomyopathy, idiopathic cardiomyopathy, and nonfailing controls
Ontology highlight
ABSTRACT: Left ventricular myocardium was snap-frozen at time of cardiac transplantation from patients with advanced idiopathic or ischemic cardiomyopathy, or at time of harvest from unused donor heart that serve as a nonfailing control. No subjects received mechanical support devices. Keywords: disease state analysis (case:control)
Project description:Left ventricular myocardium was snap-frozen at time of cardiac transplantation from patients with advanced idiopathic or ischemic cardiomyopathy, or at time of harvest from unused donor heart that serve as a nonfailing control. No subjects received mechanical support devices. Experiment Overall Design: All arrays were normalized together using RMA (www.Bioconductor.org)
Project description:Pathologically elevated mechanical load promotes the adverse remodeling of left ventricle (LV) post myocardial infarction, which results in the progression from ischemic cardiomyopathy to heart failure. Cardiac patches could attenuate adverse LV remodeling by providing mechanical support to infarcted and border zone myocardium. However, the mechanism of the translation from mechanical effects to favorable therapeutic outcome is still not clear. This study aims to strengthen the foundation of the theory of cardiac patch treatment. By transcriptome analysis, we found that the myocardial transcription levels of mechanosensitive ion channel proteins Piezo1 and Piezo2 significantly increased in patients with ischemic cardiomyopathy. In vitro tensile tests with local tissue information and finite element modeling revealed a significant decrease in local strain and mechanical load in rat infarcts and sheep LV. Cardiac function and geometry were preserved compared to non-treated control. Further, in LV myocardium of the patch-treated group, MI induced expression levels of Piezo1/2 were significantly reverted to the similar levels of the control group, indicating that Piezo1/2 are key contributors as mechanosensor which initiated the signaling cascade and translated the beneficial mechanical support to therapeutic effects. These findings demonstrated the potential of cardiac patches in treating ICM patients with remodeling risks, and could provide guidance for improvement in next generation of patch devices.
Project description:To understand the interplay between cardiomyocyte and nonmyocyte cell types in human obstructive and non-obstructive hypertrophic cardiomyopathy, single nuclei RNA-sequencing was performed on 2 unused donor hearts, 1 obstructive HCM specimen, and 6 non-obstructive HCM specimens.
Project description:Restricted access to human left ventricular myocardium is a significant limitation in the study of heart failure (HF). Here, we utilise a large human heart biobank of carefully procured, cryopreserved left ventricular myocardium to obtain direct molecular insights into ischaemic (ICM) and dilated cardiomyopathy (DCM), the most common causes of HF worldwide1. We performed unbiased, deep proteomic and metabolomic analyses of 51 left ventricular (LV) samples from 44 cryopreserved human ICM and DCM hearts, including age-matched, histopathologically normal, donor controls of both genders for comparison. For the first time, we report perturbed thyroid hormone signalling pathways in the myocardium of both types of HF, and unveil the interaction of gender with HF, including increased nitric oxide-related arginine metabolism in male hearts, and many gender-specific mitochondrial and X chromosome-linked protein and metabolite changes. We provide all raw data, in addition to an interactive online application, as a publicly-available resource.
Project description:Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy primarily of the right ventricle characterized through fibrofatty replacement of cardiomyocytes. The genetic etiology in ARVC patients is most commonly caused by dominant inheritance and high genetic heterogeneity. Though histological examinations of ARVC affected human myocardium reveals fibrolipomatous replacement, the molecular mechanisms leading to loss of cardiomyocytes are largely unknown. We therefore analyzed the transcriptomes of 6 ARVC specimen derived from heart transplantation candidates and compared our findings to 6 non-failing donor hearts (NF) which could not be transplanted for technical reasons. In addition, we compared our findings to 7 hearts from patients with idiopathic dilated cardiomyopathy. From each heart left (LV) and right ventricular (RV) myocardial samples were analyzed by Affymetrix HG-U133 Plus 2.0 arrays, adding up to six sample groups. Unsupervised cluster analyses of the six sample groups revealed a clear separation of NF and cardiomyopathy samples. However, in contrast to the other samples, unsupervised cluster analyses revealed no distinct expression pattern in LV and RV samples from ARVC-hearts. We further identified differentially expressed transcripts using t-tests and found transcripts separating diseased and NF ventricular myocardium. Of note, in failing myocardium only about 15-16% of the genes are commonly regulated compared to NF samples. In addition both cardiomyopathies are clearly distinct on the transcriptome level. Comparison of the expression patterns between the failing RV and LV using a paired t-test revealed a lack of major differences between LV and RV gene expression in ARVC hearts. Microarrays were used to elucidate the differences between non-failing control hearts and those, suffering from arrhythmogenic right ventricular cardiomyopathy (ARVC).
Project description:The purpose of this study is to identify signaling pathways that are differentially regulated in Hypertrophic Cardiomyopathy (HCM), using proteomic profiling of human myocardium.
Project description:End stage heart failure due to ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) have similar characteristics, enlargement of the ventricles, relatively thin-walled ventricle, which leads to a limited contraction force and blood loading. Nevertheless, the response for present therapeutics is very variable and the prognosis is still very bad for ICM and DCM in general. Thus, the ability to differentiate the etiologies of heart failure based structural and physiological changes of the heart would be a step forward to enhance the specificity and the success of given therapy.
Project description:Characterization of plasma metabolomic profile of 15 patients with advanced heart failure referred for heart transplantation (8 patients with chronic chagasic cardiomyopathy and 7 with idiopathic dilated cardiomyopathy) and 12 heart donor individuals using gas chromatography/quadrupole time-of-flight mass spectrometry.
Project description:Characterization of plasma metabolomic profile of 15 patients with advanced heart failure referred for heart transplantation (8 patients with chronic chagasic cardiomyopathy and 7 with idiopathic dilated cardiomyopathy) and 12 heart donor individuals using gas chromatography/quadrupole time-of-flight mass spectrometry.