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: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: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: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: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.
Project description:Human patients carrying genetic mutations in RBM20 develop a clinically aggressive dilated cardiomyopathy (DCM) characterized by early onset heart failure, high mortality, and sudden death, which is recapitulated in animal models. RBM20 has two primary domains, an RNA recognition motif (RRM) that binds RNA and an arginine/serine (RS)-rich domain that mediates spliceosome assembly and nuclear localization. Reported data showed that mutations in the RS domain lead to severe DCM. Loss of the RRM domain in RBM20 has been shown to disrupt the splicing of RBM20 target transcripts but does not lead to DCM. The objectives of the present study were to determine the functional role of the RS domain in DCM and examine the mechanisms. Mice expressing RBM20 lacking the RS domain (Rbm20ΔRS) were generated using CRISPR/Cas9 technology. Male and female Rbm20ΔRS mice developed a DCM-like phenotype characterized by ventricular dilation and impaired systolic function, that is more severe in females. Splicing of RBM20 target genes, including Ttn, was disrupted in both Rbm20ΔRS and Rbm20ΔRRM mice. However, RBM20 was mis-localized to the sarcoplasm only in the hearts of Rbm20ΔRS mice, indicating that mis-localization of RBM20 rather than disrupted splicing is key in DCM pathogenesis.
