Project description:This SuperSeries is composed of the following subset Series: GSE12754: Expression data from 28 day sham and shunt atrial and ventricular tissues (set 1) GSE12755: Expression data from 28 day sham and shunt atrial tissues (set 2) Refer to individual Series
Project description:Pharmacological and gene ablation studies have demonstrated a crucial role of the caridac natriuretic peptides (NP) hormones ANF and BNP in the maintenance of cardiovascular homeostasis. Considerable effort has been focused on the elucidation of the mechanistic underlying increased atrial ANF and BNP expression and secretion. These investigations are important because under chronic congestive heart failure, the secretion of NPs although increased and beneficial, is relatively insufficient as demonstrated by the fact that patients benefit form the unloading of the heart induced by therapeutic administration of either ANF or BNP. To identify genes involved in the transcriptional response of the endocrine heart under normal and stimulated states, we conducted differential gene expression studies of the rat atria and ventricles under normal or chronic volume overload, induced by aorto-caval shunt. The left atrial appendages and left ventricular free walls were obtained from 28 day sham and shunt operated male Sprague Dawley rats. Total RNA was obtained from three pools (of two tissues) of left atria and left ventricles under sham and shunt conditions. Three biological replicates for each muscle type and condition were generated.
Project description:Pharmacological and gene ablation studies have demonstrated a crucial role of the caridac natriuretic peptides (NP) hormones ANF and BNP in the maintenance of cardiovascular homeostasis. Considerable effort has been focused on the elucidation of the mechanistic underlying increased atrial ANF and BNP expression and secretion. These investigations are important because under chronic congestive heart failure, the secretion of NPs although increased and beneficial, is relatively insufficient as demonstrated by the fact that patients benefit form the unloading of the heart induced by therapeutic administration of either ANF or BNP. To identify genes involved in the transcriptional response of the endocrine heart under normal and stimulated states, we conducted differential gene expression studies of the rat atria under normal or chronic volume overload, induced by aorto-caval shunt. The left and right atrial appendages were obtained from 28 day sham and shunt operated male Sprague Dawley rats. Total RNA was obtained from three pools (of two tissues) of right atria and left atria under sham and shunt conditions. Three biological replicates for each muscle type and condition were generated.
Project description:We analyzed time dependent global proteomic adaptations during heart failure (HF) progression in a mouse model, suffering from left ventricular pressure overload due to transverse aortic constriction (TAC), to gain deeper insights in the disease development and identify new biomarker candidates. The hearts from TAC and sham mice were examined by cardiac MRI on either day 4, 14, 21, 28, 42, and 56 after surgery (n=6 group/time point). At each time point, proteomes of the left (LV) and right ventricles (RV) of TAC and sham mice were analyzed by mass spectrometry (MS).
Project description:Note this data set has identical data files: Files GSM40994.txt and GSM40995.txt. GSE2240 contains two different experimental subsets:; 1) Comparison of atrial and ventricular gene expression (atrial tissue of patients with sinus rhythm vs. human left ventricular non-failing myocardium); The purpose of our investigation was to identify the transcriptional basis for ultrastructural and functional specialization of human atria and ventricles. Using exploratory microarray analysis (Affymetrix U133A+B), we detected 11,740 transcripts expressed in human heart, representing the most comprehensive report of the human myocardial transcriptome to date. Variation in gene expression between atria and ventricles accounted for the largest differences in this data set, as 3.300 and 2.974 transcripts showed higher expression in atria and ventricles, respectively. Functional classification based on Gene Ontology identified chamber-specific patterns of gene expression and provided molecular insights into the regional specialization of cardiomyocytes, correlating important functional pathways to transcriptional activity: Ventricular myocytes preferentially express genes satisfying contractile and energetic requirements, while atrial myocytes exhibit specific transcriptional activities related to neurohumoral function. In addition, several pro-fibrotic and apoptotic pathways were concentrated in atrial myocardium, substantiating the higher susceptibility of atria to programmed cell death and extracellular matrix remodelling observed in human and experimental animal models of heart failure. Differences in transcriptional profiles of atrial and ventricular myocardium thus provide molecular insights into myocardial cell diversity and distinct region-specific adaptations to physiological and pathophysiological conditions (Barth AS et al., Eur J Physiol, 2005). 2) Comparison of atrial gene expression in patients with permanent atrial fibrillation and sinus rhythm. Atrial fibrillation is associated with increased expression of ventricular myosin isoforms in atrial myocardium, regarded as part of a dedifferentiation process. Whether re-expression of ventricular isoforms in atrial fibrillation is restricted to transcripts encoding for contractile proteins is unknown. Therefore, this study compares atrial mRNA expression in patients with permanent atrial fibrillation to atrial mRNA expression of patients with sinus rhythm as well as to ventricular gene expression using Affymetrix U133 arrays. In atrial myocardium, we identified 1.434 genes deregulated in atrial fibrillation, the majority of which, including key elements of calcium-dependent signaling pathways, displayed down-regulation. Functional classification based on Gene Ontology provided the specific gene sets of the interdependent processes of structural, contractile and electrophysiological remodeling. In addition, we demonstrate for the first time a prominent up-regulation of transcripts involved in metabolic activities, suggesting an adaptive response to an increased metabolic demand in fibrillating atrial myocardium. Ventricular-predominant genes were five times more likely to be up-regulated in atrial fibrillation (174 genes up-regulated, 35 genes down-regulated), while atrial-specific transcripts were predominantly down-regulated (56 genes up-regulated, 564 genes down-regulated). Overall, in atrial myocardium, functional classes of genes characteristic of ventricular myocardium were found to be up-regulated (e.g. metabolic processes) while functional classes predominantly expressed in atrial myocardium were down-regulated in atrial fibrillation (e.g. signal transduction and cell communication). Therefore, dedifferentiation with adoption of a ventricular-like signature is a general feature of the fibrillating atrium, uncovering the transcriptional response pattern in pmAF (Barth AS et al., Circ Res, 2005).
Project description:Shunt infections lead to grave neurologic morbidity for patients especially when there is a delay in diagnosis. C. acnes is the third most common cause of cerebrospinal fluid (CSF) shunt infection and is underdiagnosed due to the difficulty in culturing this fastidious, slow growing pathogen. Currently the gold standard for diagnosis of CSF shunt infections is microbiologic culture, however, in the case of C. acnes diagnostic cultures may be falsely negative. Therefore, new diagnostic methods are needed. To investigate potential CSF biomarkers of C. acnes CSF shunt infection we adapted a previously published rat model of CSF shunt infection to C. acnes. We found elevated levels of IL-1β, IL-6, CCL2 and IL-10 in the CSF and brain tissues of animals implanted with C. acnes infected catheters compared to sterile controls at day 1 post-infection. We found modest increases in neutrophils in the CSF and to a greater extend the brain tissue of animals with C. acnes infection which mirrors the clinical findings in C. acnes shunt infection. Mass spectrometry revealed that the CSF proteome is altered during C. acnes shunt infection and changes over the course of infection with an acute phase and pathogen neutralization response at day 1 post-infection to a more biosynthetic and metabolic response at day 28 post-infection relating to healing. Collectively, these results demonstrate that it is possible to distinguish C. acnes infection from sterile post-operative inflammation and CSF proteins could be useful in a diagnostic strategy for this pathogen that is difficult to diagnose.
Project description:Three wild type cell lines (WTC:ACTN2-eGFP, WTC:Myl2-eGFP, SCVI114) and three genetically modified cell lines (PM28, PM52, Del33) were differentiated using two monolayer (atrial and ventricular) and two organoid (also atrial and ventricular) differentiation protocols. Cells from multiple samples at differentiation day 15 (wild type cell lines) and day 30 (all cell lines) were isolated, multiplexed using the MULTI-seq approach; subsequently library preparation (10X platform) and sequencing was performed.
Project description:A porcine microarray study of right ventricular failure due to coronary artery ligation of the right ventricular free wall and subsequent treatment of right ventricular failure by volume unloading using a shunt between superior vena cava and the pulmonary artery (Glenn-shunt) 1. Surgical preparation with a 12 mm graft between superior vena cava and pulmonary artery, the graft is then clamped - Baseline sample using a biopsy needle. 2. After surgical preparation the coronary arteries of the right ventricular free wall are ligated, then heart failure develops over 120 minutes - Failure sample using a biopsy needle. 3. The shunt is then opened and the superior vena cava closed between the shunt and right atrium, diverting the blood from superior vena cava through the shunt for a period of 15 minutes partially unloading the right ventricle - Shunt sample using a biopsy needle. A series of six pigs, three samples from each animal: baseline, failure and shunt/treatment.