Project description:Men are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM). We previously showed that immune responses in the heart are phenotypically distinct in male compared to female mice 10 days after infection resulting in severe DCM in males. Groups consisted of Infected Males, Infected Females, Uninfected Males and Uninfected females. There are 3 mice per group. A total of 12 samples were analyzed in this experiment (12 for 10 dpi and 12 for 90 dpi).
Project description:Dilated cardiomyopathy (DCM) is often driven by myocarditis, however, the underlying immune mechanism remains unknown. We performed bulk-RNA sequencing of endomyocardial biopsies taken 9 months (interquartile range 4-26 months) from DCM diagnosis and we found that in patients with high cardiac inflammation (at least 7 CD3+ T-cells per mm2 or at least 14 CD45+ leukocyte per mm2 endomyocardial biopsy) Perforin-1, Granzyme-A, Granzyme-H, and Interleukin-17 receptor subunit C were more often expressed compared to patients with low cardiac inflammation (less than 3 CD3+ T-cells per mm2 and less than 5 CD45+ leukocytes per mm2 endomyocardial biopsy).
Project description:Men are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM). We previously showed that immune responses in the heart are phenotypically distinct in male compared to female mice 10 days after infection resulting in severe DCM in males.
Project description:This project analyzes genome-wide cardiac DNA methylation in patients with idopathic DCM and control individuals Given are datafiles from n = 8 controls (patients after Htx) and n = 9 patients with idopathic DCM. The datasets have been normalized together with other beadchip files not subject to this study. Methylation profiles were generated from human left ventricular myocardium DNA.
Project description:Circular RNAs (circRNAs) have been reported to play important roles in various cardiovascular diseases. However, their expression profile in human dilated cardiomyopathy (DCM) has not been fully elucidated. In our study, heart samples from DCM patients and healthy controls were used to identify circRNAs by high-throughput sequencing. A total of 9585 circRNAs were identified in the DCM and control groups. To assess the differentially expressed circRNAs, the criteria were set as a fold change of ≥ 2 or ≤ 0.5 and a P value of < 0.05. Compared with circRNAs in the control group, 298 dysregulated circRNAs were identified in patients with DCM, of which 231 were upregulated and 85 were downregulated. In conclusion, our study evaluated cardiac circRNA expression in DCM by high-throughput sequencing and provide a foundation for future studies of circRNAs in DCM.
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
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
Project description:Dilated cardiomyopathy (DCM) entails a broad group of diseases, acquired or genetic, that share a similar phenotype. The understanding of gene-specific pathogenetic mechanisms and the determination of the functional effects of each variant may tailor different therapeutic strategies. MicroRNAs (miRNAs) are short sequences of non-coding RNA that play an important role in the development of several cardiovascular diseases, including DCM. Here, we applied mRNA and small RNA sequencing to identify the gene and miRNA signature from myocardial biopsies from four patients with DCM caused by volume overload (VCM) and four with ischemic DCM (ICM). Analysis showed five miRNAs and 112 mRNAs dysregulated in VCM vs ICM. Differentially expressed genes were positively enriched for extracellular matrix (ECM), mitochondria respiration-related, cardiac muscle contraction and fatty acid pathways in VCM vs ICM, and negatively enriched for immune response-related pathways, JAK-STAT and NF-kappa B signaling pathways in VCM vs ICM. miRNA-mRNA interaction analysis revealed four negatively correlated miRNA-target transcript pairs, miR-218-5p-DDX6, miR-218-5p-TT39C, miR-218-5p-SEMA4A and miR-494-3p-SGMS2. qRT-PCR validation showed a strong correlation between RNA-seq and qRT-PCR for these genes and miRNAs. These findings suggest that transcriptome signatures may distinguish distinct etiologies of DCM shedding light on underlying biological differences between VCM and ICM.
Project description:To investigate the physiological characteristics of cardiac fibroblasts (CF) from pediatric dilated cardiomyopathy (DCM) patients, CFs were harvested from left ventricular free wall at the heart transplantation. We then performed RNA-seq for 7 different lines of CFs.
