Novel heart specific long non-coding RNAs contribute to pathogenesis of Arrhythmogenic Cardiomyopathy [ARVC patients' heart LV]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE107311 | GEO | 2020/01/01
REPOSITORIES: GEO
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Project description:Arrhythmogenic cardiomyopathy (AC) is an inherited cardiomyopathy characterized by fibrofatty replacement predominantly involved in right ventricle and clinically by ventricular arrhythmias.In this study, we set out to characterize the cardiac novel long-noncoding RNAs using deep RNA sequencing data from human heart tissues. Particularly, we identified AC specific novel lncRNAs that contribute to AC pathophysiology by comparing the lncRNAs transcripts of nine AC explanted hearts (RV), five non-diseased donor hearts (RV), four non-AC failing hearts (dilated cardiomyopathy, RV). To dissect the roles of novel lncRNAs in ARVC from LV, we also include six non-diseased donor hearts (LV) and six ARVC explanted hearts (LV) in the analysis. In the identified novel AC lncRNAs, a large part of them are derived from enhancer regions and acting as cis- elements to potentially regulate lipogenesis or lipid metabolism related genes. Finally, we validated several of these AC specific novel lncRNAs and their potential targets in independent patient samples. Collectively, we identified high-confidence AC specific novel lncRNAs from human samples and suggest their potential roles as cis- elements in AC pathology. Further study of these novel AC lncRNAs could provide new opportunities for diagnosis and therapeutic intervention.
2020-01-01 | GSE107475 | GEO
Project description:Arrhythmogenic cardiomyopathy (AC) is an inherited cardiomyopathy characterized by fibrofatty replacement predominantly involved in right ventricle and clinically by ventricular arrhythmias.In this study, we set out to characterize the cardiac novel long-noncoding RNAs using deep RNA sequencing data from human heart tissues. Particularly, we identified AC specific novel lncRNAs that contribute to AC pathophysiology by comparing the lncRNAs transcripts of nine AC explanted hearts (RV), five non-diseased donor hearts (RV), four non-AC failing hearts (dilated cardiomyopathy, RV). To dissect the roles of novel lncRNAs in ARVC from LV, we also include six non-diseased donor hearts (LV) and six ARVC explanted hearts (LV) in the analysis. In the identified novel AC lncRNAs, a large part of them are derived from enhancer regions and acting as cis- elements to potentially regulate lipogenesis or lipid metabolism related genes. Finally, we validated several of these AC specific novel lncRNAs and their potential targets in independent patient samples. Collectively, we identified high-confidence AC specific novel lncRNAs from human samples and suggest their potential roles as cis- elements in AC pathology. Further study of these novel AC lncRNAs could provide new opportunities for diagnosis and therapeutic intervention.
2020-11-20 | GSE107156 | GEO
Project description:Arrhythmogenic cardiomyopathy (AC) is an inherited cardiomyopathy characterized by fibrofatty replacement predominantly involved in right ventricle and clinically by ventricular arrhythmias.In this study, we set out to characterize the cardiac novel long-noncoding RNAs using deep RNA sequencing data from human heart tissues. Particularly, we identified AC specific novel lncRNAs that contribute to AC pathophysiology by comparing the lncRNAs transcripts of nine AC explanted hearts (RV), five non-diseased donor hearts (RV), four non-AC failing hearts (dilated cardiomyopathy, RV). To dissect the roles of novel lncRNAs in ARVC from LV, we also include six non-diseased donor hearts (LV) and six ARVC explanted hearts (LV) in the analysis. In the identified novel AC lncRNAs, a large part of them are derived from enhancer regions and acting as cis- elements to potentially regulate lipogenesis or lipid metabolism related genes. Finally, we validated several of these AC specific novel lncRNAs and their potential targets in independent patient samples. Collectively, we identified high-confidence AC specific novel lncRNAs from human samples and suggest their potential roles as cis- elements in AC pathology. Further study of these novel AC lncRNAs could provide new opportunities for diagnosis and therapeutic intervention.
2020-11-20 | GSE107125 | GEO
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).
2011-11-30 | E-GEOD-29819 | biostudies-arrayexpress
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.
2011-11-30 | GSE29819 | GEO
Project description:We reported the RNAseq analyses of right ventricle (RV) and left ventricle (LV) in neonatal volume overload (VO) and sham-operated SD rat. VO was induced by the fistula between abdominal aorta and inferior vena cava (AVF) within 24 hours postnatally (P1). RNAseq analyses of RV and LV free wall of P7 from VO and sham-operated rat. It demonstrated that the 1806 differentially expressed genes (DEGs) between RV and LV at the neonatal stage were primarily enriched in GTPase mediating signal transduction, insulin signaling pathway and thyroid hormone signaling pathway. VO produced 3 more times DEGs in LV than RV . GO analysis of these DEGs demonstrated that in the top 150 enriched terms, the LV comparison and RV comparison shared 34 terms (22.7%) in common. These commonly enriched terms were primarily associated with GTPase mediating signal transduction. KEGG analysis of these DEGs demonstrated that in the top 30 enriched terms, the LV comparison and RV comparison shared 14 terms (46.7%) in common. And insulin signaling pathway and thyroid hormone signaling pathway are the top two enriched terms in common. Regarding the differently enriched GO terms, they were primarily associated with lipid metabolism and ion channel in RV and primarily associated nucleic acid metabolism in LV. The top two differently enriched KEGG terms were arrhythmogenic right ventricular cardiomyopathy (ARVC) and adipocytokine signaling pathway in RV while microRNAs in cancer and longevity regulating pathway in LV. These results were further confirmed by the determination of metabolites.
2022-12-15 | GSE186247 | GEO
Project description:We examine the RNA profile of LV and RV in donor heart with different period of storage (0, 4, and 8 hours) follwed by reperfusion. We find that both LV and RV has activated immune response after prolonged storage compared to 0h.
2021-09-08 | GSE174342 | GEO
Project description:Background: Right ventricular (RV) and left ventricular (LV) myocardium differ in their response to pressure-overload hypertrophy (POH). In this report we use microarray and proteomic analyses to identify pathways modulated by LV-, and RV-POH in the immature heart. Methods: Newborn New Zealand White rabbits underwent banding of the descending thoracic aorta (LV-POH; n=6). RV-POH was achieved by banding the pulmonary artery (n=6). Sham–control animals (SC; n=6 each) were sham-manipulated. Following 4 (LV-POH) and 6 weeks (RV-POH) recovery, the hearts were removed and matched sample RNA and proteins were isolated for microarray and proteomic analysis. Results: There was no difference in body weight in RV-, LV-POH vs. SC but there was a significant increase vs. SC in RV (3.2±0.8g vs. 1.2±0.3g; P<0.01) and LV weight (7.08±0.6g vs. 4.02±0.2g; P<0.01). Fractional area change (RV-POH) and shortening fraction (LV-POH) decreased significantly (23±6 vs. 47±6 and 21±4 vs.44±2, respectively, P<0.01). Microarray analysis demonstrated that LV-POH enriched pathways for oxidative phosphorylation, mitochondria energy pathways, actin, ILK, hypoxia, calcium and protein kinase-A signalling. RV-POH enriched pathways for cardiac oxidative phosphorylation. Proteomic analysis revealed 19 proteins were uniquely expressed in LV-POH vs. SC. Functional annotation clustering analysis indicated significant enrichment for the mitochondrion, cellular macromolecular complex assembly and oxidative phosphorylation. RV-POH had 15 uniquely expressed proteins vs. SC. Functional annotation clustering analysis indicated significant enrichment in structural constituents of muscle, cardiac muscle tissue development and calcium handling. Conclusion: Our results identify unique transcript and protein expression profiles in LV, RV-POH and provide new insight into the biological basis of ventricular specific hypertrophy. 3 different conditions: PAB-RV vs. Sham-control RV, PAB-RV [test] vs. PAB-LV [control], AOB-LV vs. Sham-control LV.
2011-06-24 | E-GEOD-30194 | biostudies-arrayexpress
Project description:The goal of this experiment was to identify gene expression changes that are common in different heart failure (HF) types or specific to an etiology of HF. HF groups studied include doxorubicin induced cardiomyopathy, familial dilated cardiomyopathy, hypertrophic cardiomyopathy, idiopathic dilated cardiomyopathy, ischemic heart disease, peripartum cardiomyopathy, and viral induced cardiomyopathy. Non-diseased left ventricles (LV) were obtained from donor hearts not used for transplantation (these were considered to be unsuitable for transplantation for a variety of reasons including the lack of a tissue-compatible recipient). Failing LV were obtained from patients undergoing heart transplantation. Transmural sections of LV anterior free wall were trimmed of fat, dissected into 1-1.5 gm pieces, and immediately frozen in the operating theater. 100-200 mg of frozen transmural LV was ground to a fine powder in liquid nitrogen using a mortar and pestle. Then total RNA was isolated by a method described by Wei and Khan (A Molecular Cloning Manual). The purity of the RNA extract was assessed by measuring the absorbance at 260 nm and 280 nm. Its quantity and integrity was then examined using RNA Nano Chips on a 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA, USA). 10 ?g of RNA extracts and a universal human reference RNA (Stratagene, La Jolla, CA, USA) were reverse transcribed with Cy3-dUTP and Cy5-dUTP, respectively, to produce labeled cDNA probes using Thermoscript reverse transcriptase according Hwang JJ et. al. (Physiological Genomics 10: 31-44, 2002). Raw scanned images were processed using ScanAlyze version 2.50 (Michael Eisen, Stanford University, CA, USA). Cy3 and Cy5 scans were superimposed, local backgrounds were subtracted, and the fluorescence intensities of each spot were quantified. All further analyses of CardioChips were done using GeneSpring version 6.1 (Silicon Genetics, Redwood City, CA, USA). The data from each array was normalized first to the reference RNA and then a LOWESS curve was fit to the log-intensity versus log-ratio plot for each array and for each gene across all experiments. 40.0% of the data was used to calculate the LOWESS fit at each point. Differentially expressed genes in each HF group compared to donor hearts were identified by a one-way ANOVA test (P <0.05) with the benjamini and hochberg multiple testing corrections and we selected those genes with an average difference greater than 1.5 fold. A hierarchical clustering analysis was performed using pearson correlation with the separation ratio of 1.0 and minimum distance of 0.001 as similarity measure. Using a cardiovascular-specific gene array (CardioChip) of 42 heart failure (HF) patients from a wide range of etiology groups and 8 non-failing donors, we have identified down-regulation of LIM domain protein which may be an important pathway for the clinical progression of HF. We identified six genes, encoding LIM domain and Homer proteins, that are down-regulated in terminally failing hearts. The LIM and cysteine rich domain 1 (LMCD1) gene, in particular, was significantly down-regulated in all HF samples. This novel finding suggests that the LMCD 1 is a universal biomarker for end-stage HF. Other LIM domain genes were also down-regulated but only in non-familial dilated forms of cardiomyopathy. This is probably due to the fact that down-regulation of LIM protein expression may disrupt the cytoskeletal architecture, leading to dilated cardiomyopathy. In addition to identifying the LIM domain genes as possible regulatory genes involved in HF, we also demonstrated that the gene expression profile was able to classify multiple HF patients groups. This paper is the first to examine viral-induced cardiomyopathy, doxorubicin toxicity cardiomyopathy and perimartum cardiomyopathy and to perform the clustering analysis of those HF types providing new insights into human HF.
2010-06-10 | E-GEOD-2656 | biostudies-arrayexpress
Project description:Arrhythmogenic Right Ventricular Cardiomyopathy is a congenital heart disorder characterized by fibrofatty replacement of the myocardium. The exact molecular mechanisms underlying the disease remain to be elucidated and treatment options are limited. The sa12692 mutant line contains a splice site mutation in the plakoglobin gene, resulting in the expression of a truncated protein. This protein is highly similar to the protein expressed in Naxos disease, a recessive form of ARVC. RNA-seq was used to investigate the effect of the sa12692 mutation on gene expression in order to uncover signalling pathways involved in the pathogenesis of ARVC. Gene expression was examined in whole larvae at 5 dpf and in hearts of 1 year old adult fish. Larvae at 5 dpf were selected as this timepoint is equivalent to birth in humans. Adult hearts were selected as ARVC is a disorder of the heart and cardiac symptoms generally manifest in adulthood. Hence, the molecular effect of the mutation could be profiled at two life stages.
2021-04-30 | E-MTAB-7920 | biostudies-arrayexpress