Circulating Long Non-coding RNA ENST00000507296 is a Prognostic Indicator in Patients with Dilated Cardiomyopathy
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ABSTRACT:
PROVIDER: PRJNA511960 | ENA |
REPOSITORIES: ENA
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Project description:Dilated cardiomyopathy vs Myocarditis
| PRJNA493608 | ENA
Project description:There is an emerging hypothesis that dilated cardiomyopathy (DCM) is a manifestation of end-stage heart failure (ESHF) resulting from “final common pathway” despite heterogeneous primary etiologies. We performed genome-wide expression profiling by means of high-density oligonucleotide microarrays using cardiac muscles from patients with DCM or specific cardiomyopathy as well as non-disease control hearts. Differentially expressed genes between ESHF and non-disease samples should include both genes reactive to heart failure (HF) and those responsible for ESHF. With the aid of samples with acute HF without DCM and those with DCM without HF (corrected with left ventricular assist device), we successfully distinguished ESHF genes from HF genes. Our findings implicate that transcriptional signature of cardiac muscle can be potentially applied as a diagnostic or prognostic tool for severe HF. Keywords: disease state analysis
2008-01-09 | GSE9800 | GEO
Project description:Background - Cardiac microRNAs (miRNAs) could be released into circulation thus becoming circulating cardiac miRNAs, which are increasingly recognized as noninvasive and readily accessible biomarker for multiple heart diseases. A global loss of cardiac miRNAs due to dicer or dgcr8 depletion has been reported to lead to dilated cardiomyopathy (DCM). However, DCM-associated circulating miRNAs (DACMs) and their roles in regulating DCM progression remain largely unexplored. Methods and Results - Through miRNA sequencing of human plasma procured from DCM patients and healthy control people, DCM was characterized with a unique expression pattern for circulating miRNAs. Among them, miR-26a-5p, miR-30c-5p, miR-126-5p, and miR-126-3p were all identified with dramatic reductions in DCM mouse myocardium as in the plasma of DCM patients. FOXO3, highlighted as a predicted common target gene, was experimentally demonstrated to be repressed within cardiomyocytes by these miRNAs except miR-26a-5p. Mechanistically, miRNA combination (miR-30c-5p, miR-126-5p, and miR-126-3p) significantly attenuated FOXO3-induced apoptosis and autophagy observed in cardiomyocytes as well as in DCM murine heart. Cardiac-specific knockout of FOXO3 conspicuously mitigated myocardial apoptosis and autophagy in DCM development. Moreover, stymieing the interaction between these miRNAs and FOXO3 mRNA extremely crippled the cardioprotection of these miRNAs against DCM progression. Cardiac miRNA-FOXO3 axis plays a pivotal role in safeguarding against myocardial apoptosis and autophagy, thereby maintaining cardiac homeostasis and potently preventing DCM development. These findings may provide serological clues for the noninvasive diagnosis of DCM in the future, and unambiguously shed new light on DCM pathogenesis and associated therapeutic targets
2022-07-31 | GSE209991 | GEO
Project description:This study attempts at investigating the changes in cardiac gene expression that occur in Dilated Cardiomyopathy (DCM). DCM in Dobermans and Boxers are the focus of this study. Control heart tissue as well as Pacing tissue used is from mongrel dogs. Keywords: control vs pacing vs disease; strain specific disease 3 Dobermans-DCM, 4 Boxers-DCM, 3 mongrels-control and 3 mongrels-pacing
2008-05-08 | E-GEOD-11015 | biostudies-arrayexpress
Project description:Dilated cardiomyopathy (DCM) is a common cause of heart failure and a leading cause of cardiac transplantation in western countries. The robust predictive expression profile of cardiomyopathic and NF hearts as well as the functional classification can help to identify promising candidates for DCM and may improve the early diagnosis of cardiomyopathy. Keywords: disease state analysis
2006-08-01 | GSE3585 | GEO
Project description:Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy and main indication for heart transplantation in children. Therapies specific to pediatric DCM remains limited due to lack of a disease model. Our previous study showed that treatment of neonatal rat ventricular myocytes (NRVMs) with non-failing or DCM pediatric patient serum activates the fetal gene program (FGP). Here we show that serum treatment with Proteinase K prevents activation of the FGP, whereas RNase treatment exacerbates it, suggesting that circulating proteins, but not circulating microRNAs, promote these pathological changes. Evaluation of the protein secretome showed that midkine (MDK) is up-regulated in DCM serum, and NRVM treatment with MDK activates the FGP. Changes in gene expression in serum-treated NRVMs, evaluated by next-generation RNA sequencing (RNA-Seq), indicates extracellular matrix remodeling and focal adhesion pathways are upregulated in pediatric DCM serum and serum-treated NRVMs, suggesting alterations in cellular stiffness. Cellular stiffness was evaluated by Atomic Force Microscopy, which showed an increase in stiffness in DCM serum-treated NRVMs. Of the proteins increased in DCM sera, secreted frizzled related protein 1 (sFRP1) was a potential candidate for the increase in cellular stiffness, and sFRP1 treatment of NRVMs recapitulated the increase in cellular stiffness observed in response to DCM-serum treatment. Our results show that serum circulating proteins promote pathological changes in gene expression and cellular stiffness, and circulating miRNAs are protective against pathological changes.
2021-07-31 | GSE181048 | GEO
Project description:Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy and main indication for heart transplantation in children. Therapies specific to pediatric DCM remains limited due to lack of a disease model. Our previous study showed that treatment of neonatal rat ventricular myocytes (NRVMs) with non-failing or DCM pediatric patient serum activates the fetal gene program (FGP). Here we show that serum treatment with Proteinase K prevents activation of the FGP, whereas RNase treatment exacerbates it, suggesting that circulating proteins, but not circulating microRNAs, promote these pathological changes. Evaluation of the protein secretome showed that midkine (MDK) is up-regulated in DCM serum, and NRVM treatment with MDK activates the FGP. Changes in gene expression in serum-treated NRVMs, evaluated by next-generation RNA sequencing (RNA-Seq), indicates extracellular matrix remodeling and focal adhesion pathways are upregulated in pediatric DCM serum and serum-treated NRVMs, suggesting alterations in cellular stiffness. Cellular stiffness was evaluated by Atomic Force Microscopy, which showed an increase in stiffness in DCM serum-treated NRVMs. Of the proteins increased in DCM sera, secreted frizzled related protein 1 (sFRP1) was a potential candidate for the increase in cellular stiffness, and sFRP1 treatment of NRVMs recapitulated the increase in cellular stiffness observed in response to DCM-serum treatment. Our results show that serum circulating proteins promote pathological changes in gene expression and cellular stiffness, and circulating miRNAs are protective against pathological changes.
2021-07-31 | GSE181091 | GEO
Project description:Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy and main indication for heart transplantation in children. Therapies specific to pediatric DCM remains limited due to lack of a disease model. Our previous study showed that treatment of neonatal rat ventricular myocytes (NRVMs) with non-failing or DCM pediatric patient serum activates the fetal gene program (FGP). Here we show that serum treatment with Proteinase K prevents activation of the FGP, whereas RNase treatment exacerbates it, suggesting that circulating proteins, but not circulating microRNAs, promote these pathological changes. Evaluation of the protein secretome showed that midkine (MDK) is up-regulated in DCM serum, and NRVM treatment with MDK activates the FGP. Changes in gene expression in serum-treated NRVMs, evaluated by next-generation RNA sequencing (RNA-Seq), indicates extracellular matrix remodeling and focal adhesion pathways are upregulated in pediatric DCM serum and serum-treated NRVMs, suggesting alterations in cellular stiffness. Cellular stiffness was evaluated by Atomic Force Microscopy, which showed an increase in stiffness in DCM serum-treated NRVMs. Of the proteins increased in DCM sera, secreted frizzled related protein 1 (sFRP1) was a potential candidate for the increase in cellular stiffness, and sFRP1 treatment of NRVMs recapitulated the increase in cellular stiffness observed in response to DCM-serum treatment. Our results show that serum circulating proteins promote pathological changes in gene expression and cellular stiffness, and circulating miRNAs are protective against pathological changes.
2021-07-31 | GSE181033 | GEO
Project description:Cardiac metabolism is deranged in heart failure, but underlying mechanisms remain unclear. Lysine demethylase 8 (Kdm8) represses gene expression in the embryo and controls metabolism in cancer. However, its function in cardiac homeostasis is unknown. We show that Kdm8 maintains a mitochondrial gene network active by repressing Tbx15 to prevent dilated cardiomyopathy leading to lethal heart failure. Deletion of Kdm8 in mouse cardiomyocytes increased H3K36me2 with activation of Tbx15 and repression of target genes in the NAD+ pathway before dilated cardiomyopathy initiates. Moreover, NAD+ supplementation prevented dilated cardiomyopathy in Kdm8 mutant mice and TBX15 overexpression blunted NAD+-activated cardiomyocyte respiration. Furthermore, KDM8 was downregulated in human hearts affected by dilated cardiomyopathy and higher TBX15 expression defines a subgroup of affected hearts with the strongest downregulation of genes encoding mitochondrial proteins. Thus, KDM8 represses TBX15 to maintain cardiac metabolism. Our results suggest that epigenetic dysregulation of metabolic gene networks initiates myocardium deterioration towards heart failure and could underlie heterogeneity of dilated cardiomyopathy.
2022-12-23 | GSE215793 | GEO
Project description:Cardiac metabolism is deranged in heart failure, but underlying mechanisms remain unclear. Lysine demethylase 8 (Kdm8) represses gene expression in the embryo and controls metabolism in cancer. However, its function in cardiac homeostasis is unknown. We show that Kdm8 maintains a mitochondrial gene network active by repressing Tbx15 to prevent dilated cardiomyopathy leading to lethal heart failure. Deletion of Kdm8 in mouse cardiomyocytes increased H3K36me2 with activation of Tbx15 and repression of target genes in the NAD+ pathway before dilated cardiomyopathy initiates. Moreover, NAD+ supplementation prevented dilated cardiomyopathy in Kdm8 mutant mice and TBX15 overexpression blunted NAD+-activated cardiomyocyte respiration. Furthermore, KDM8 was downregulated in human hearts affected by dilated cardiomyopathy and higher TBX15 expression defines a subgroup of affected hearts with the strongest downregulation of genes encoding mitochondrial proteins. Thus, KDM8 represses TBX15 to maintain cardiac metabolism. Our results suggest that epigenetic dysregulation of metabolic gene networks initiates myocardium deterioration towards heart failure and could underlie heterogeneity of dilated cardiomyopathy.
2022-12-23 | GSE215351 | GEO