Radiation-induced Circulating microRNAs predict cardiac dysfunction after radiotherapy
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE225243 | GEO | 2023/05/07
REPOSITORIES: GEO
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Project description:Poor maternal nutrition causes intrauterine growth restriction (IUGR); however, its effects on fetal cardiac development are unclear. We have developed a baboon model of moderate maternal undernutrition, leading to IUGR. We hypothesized that the IUGR affects fetal cardiac structure and metabolism. Six control pregnant baboons ate ad-libitum (CTRL)) or 70% CTRL from 0.16 of gestation (G). Fetuses were euthanized at C-section at 0.9G under general anesthesia. Male but not female IUGR fetuses showed left ventricular fibrosis inversely correlated with birth weight. Expression of extracellular matrix protein TSP-1 was increased (p<0.05) in male IUGR. Expression of cardiac fibrotic markers TGFß, SMAD3 and ALK-1 were downregulated in male IUGRs with no difference in females. Autophagy was present in male IUGR evidenced by upregulation of ATG7 expression and lipidation LC3B. Global miRNA expression profiling revealed 56 annotated and novel cardiac miRNAs exclusively dysregulated in female IUGR, and 38 cardiac miRNAs were exclusively dysregulated in males (p<0.05). Fifteen (CTRL) and 23 (IUGR) miRNAs, were differentially expressed between males and females (p<0.05) suggesting sexual dimorphism, which can be at least partially explained by differential expression of upstream transcription factors (e.g. HNF4a, and NF?B p50). Lipidomics analysis of fetal cardiac tissue exhibited a net increase in diacylglycerol and plasmalogens and a decrease in triglycerides and phosphatidylcholines. In summary, IUGR resulting from decreased maternal nutrition is associated with sex-dependent dysregulations in cardiac structure, miRNA expression, and lipid metabolism. If these changes persist postnatally, they may program offspring for higher later life cardiac risk.
2018-04-30 | MTBLS426 | MetaboLights
Project description:This study describes a circulating miRNA signature of unstable angina (UA), which may be used as a novel biomarker for unstable coronary artery disease (CAD). The Taqman low-density miRNA array were used to identify distinct miRNA expression profiles in the plasma of patients with typical UA and angiographically documented CAD (UA group, n = 13) compared to individuals with non-cardiac chest pain (control group, n = 13). EDTA-plasma samples were obtained before the cardiac catheterization procedure.The study included 2 groups that were classified according to angiographic evidence and clinical evaluation of chest pain. Patients with chest pain or discomfort but with angiographic exclusion of coronary atherosclerosis were enrolled in the control group (n = 13). Chest discomfort referred to the following complaints: chest pain, pressure, tightness, or heaviness; pain that radiated to the neck, jaw, shoulders, back, or one or both arms; and persistent shortness of breath. Patients with typical unstable angina (UA) and angiographically documented CAD were enrolled in the UA group (n = 13).
2013-08-13 | E-GEOD-49823 | biostudies-arrayexpress
Project description:To investigate changes in cardiac transcription profiles caused by on-pump cardiac surgery, we collected myocardial samples, prior and after grafting, from patients undergoing on-pump coronary artery bypass grafting with cardiopulmonary bypass and cardiac arrest. The transcriptional profile of the mRNA in these samples was measured with gene array technology. Changes in transcriptional profiles can be correlated with the stress response of heart to surgery, cardiopulmonary bypass and cardiac arrest. Keywords: human, cardiac, CABG coronary surgery, gene expression, cardiopulmonary bypass. Myocardial samples were collected, prior and after grafting, from patients undergoing on-pump coronary artery bypass grafting with cardiopulmonary bypass and cardiac arrest.
2010-07-07 | E-GEOD-12486 | biostudies-arrayexpress
Project description:DEAD-box RNA-binding proteins (RBPs) play a significant role in RNA metabolism to achieve cellular homeostasis, including miRNA biogenesis and transcription. Hypoxia induces stemness cell-like characteristics in cancer cells and promotes malignant progression. Despite the fact that hypoxia can induce the changes in protein and RNA modification, thereby regulating downstream gene expressions, how modifications at different molecular layers interplay with each other are poorly understood. Here we show that hypoxia induces HectH9-mediated K63-linked polyubiquitination of the DEAD-box protein DDX17 as well as reduces N6-methyladenosine (m6A) marks in pri-miRNAs. While m6A potentiates DDX17 binding to pri-miRNAs, decreased m6A modifications of pri-miRNAs and increased polyubiquitination of DDX17 under hypoxia lead to decreased DDX17 binding to pri-miRNAs binding. These events enhance the association of DDX17 with the ubiquitin receptor p300 and lead to a decrease in miRNA biogenesis, especially for miRNAs regulating stemness and stemness-related genes. In addition, polyubiquitinated DDX17 together with p300 upregulates H3K56Ac levels on the stemness and stemness-related genes, resulting in enhancement of tumor initiating ability. Post-transcriptionally, decreased miRNA production, including those targeting stemness genes or stemness-related genes, also facilitates tumor initiation. Together, hypoxia triggers DDX17 poly-ubiquitination, which orchestrates dual mechanisms to increase tumor initiating ability and promote tumor progression.
2018-03-09 | PXD006059 | JPOST Repository
Project description:As the fetal heart develops, cardiomyocyte proliferation potential decreases while fatty acid oxidative capacity increases, a highly regulated transition known as cardiac maturation. Small noncoding RNAs, such as microRNAs (miRNAs), contribute to the establishment and control of tissue-specific transcriptional programs. However, small RNA expression dynamics and genome wide miRNA regulatory networks controlling maturation of the human fetal heart remain poorly understood. Transcriptome profiling of small RNAs revealed the temporal expression patterns of miRNA, piRNA, circRNA, snoRNA, snRNA and tRNA in the developing human heart between 8 and 19 weeks of gestation. Our analysis revealed that miRNAs were the most dynamically expressed small RNA species throughout mid-gestation. Cross-referencing differentially expressed miRNAs and mRNAs predicted 6,200 mRNA targets, 2134 of which were upregulated and 4066 downregulated as gestation progresses. Moreover, we found that downregulated targets of upregulated miRNAs predominantly control cell cycle progression, while upregulated targets of downregulated miRNAs are linked to energy sensing and oxidative metabolism. Furthermore, integration of miRNA and mRNA profiles with proteomes and reporter metabolites revealed that proteins encoded in mRNA targets, and their associated metabolites, mediate fatty acid oxidation and are enriched as the heart develops.This study revealed the small RNAome of the maturing human fetal heart. Furthermore, our findings suggest that coordinated activation and repression of miRNA expression throughout mid-gestation is essential to establish a dynamic miRNA-mRNA-protein network that decreases cardiomyocyte proliferation potential while increasing the oxidative capacity of the maturing human fetal heart.
2024-01-26 | PXD044936 | Pride
Project description:To investigate changes in cardiac transcription profiles caused by on-pump cardiac surgery, we collected myocardial samples, prior and after grafting, from patients undergoing on-pump coronary artery bypass grafting with cardiopulmonary bypass and cardiac arrest. The transcriptional profile of the mRNA in these samples was measured with gene array technology. Changes in transcriptional profiles can be correlated with the stress response of heart to surgery, cardiopulmonary bypass and cardiac arrest. Keywords: human, cardiac, CABG coronary surgery, gene expression, cardiopulmonary bypass.
2010-06-22 | GSE12486 | GEO
Project description:This data set was downloaded from MetaboLights (http://www.ebi.ac.uk/metabolights/) accession number MTBLS426 Abstract:Poor maternal nutrition causes intrauterine growth restriction (IUGR); however, its effects on fetal cardiac development are unclear. We have developed a baboon model of moderate maternal undernutrition, leading to IUGR. We hypothesized that the IUGR affects fetal cardiac structure and metabolism. Six control pregnant baboons ate ad-libitum (CTRL)) or 70% CTRL from 0.16 of gestation (G). Fetuses were euthanized at C-section at 0.9G under general anesthesia. Male but not female IUGR fetuses showed left ventricular fibrosis inversely correlated with birth weight. Expression of extracellular matrix protein TSP-1 was increased (p<0.05) in male IUGR. Expression of cardiac fibrotic markers TGFß, SMAD3 and ALK-1 were downregulated in male IUGRs with no difference in females. Autophagy was present in male IUGR evidenced by upregulation of ATG7 expression and lipidation LC3B. Global miRNA expression profiling revealed 56 annotated and novel cardiac miRNAs exclusively dysregulated in female IUGR, and 38 cardiac miRNAs were exclusively dysregulated in males (p<0.05). Fifteen (CTRL) and 23 (IUGR) miRNAs, were differentially expressed between males and females (p<0.05) suggesting sexual dimorphism, which can be at least partially explained by differential expression of upstream transcription factors (e.g. HNF4a, and NF?B p50). Lipidomics analysis of fetal cardiac tissue exhibited a net increase in diacylglycerol and plasmalogens and a decrease in triglycerides and phosphatidylcholines. In summary, IUGR resulting from decreased maternal nutrition is associated with sex-dependent dysregulations in cardiac structure, miRNA expression, and lipid metabolism. If these changes persist postnatally, they may program offspring for higher later life cardiac risk.
2018-08-07 | MSV000082776 | GNPS
Project description:This study describes a circulating miRNA signature of unstable angina (UA), which may be used as a novel biomarker for unstable coronary artery disease (CAD). The Taqman low-density miRNA array were used to identify distinct miRNA expression profiles in the plasma of patients with typical UA and angiographically documented CAD (UA group, n = 13) compared to individuals with non-cardiac chest pain (control group, n = 13).
2013-08-13 | GSE49823 | GEO
Project description:In this study, we aimed to demonstrate expression profiles of circulating microRNAs (miRNAs) in dogs with eccentric or concentric cardiac hypertrophy, and investigate whether there is a difference in miRNA expression according to the type of cardiac hypertrophy. Dogs with myxomatous mitral valve degeneration (MMVD) or pulmonic stenosis (PS) were included in this study, which are the two representative diseases of eccentric or concentric cardiac hypertrophy in dogs, respectively. Circulating miRNAs were isolated from the serum samples of five dogs with MMVD, five dogs with PS, and five healthy dogs. The circulating miRNA expression levels of dogs with MMVD or PS were compared with those of the healthy dogs by microarray analysis (Affymetrix GeneChip miRNA 4.0), using two independent parameters, a fold change cut-off of > 1.5 (up or down regulation) and p-value of < 0.05.
2021-03-24 | E-MTAB-10029 | biostudies-arrayexpress
Project description:The purpose of the present study was to investigate the activation of the cardiac inflammatory response in the hearts of SHAM (surgical opening of the chest) mice in comparison to CONTROL hearts isolated from naïve (not operated) mice. Male C57BL/6J (10 weeks) were subjected to an open-chest ischemia-reperfusion (I/R) SHAM procedure in order to examine the effects of this surgery alone in producing cardiac inflammation. The procedure consisted of thoracotomy and a suture passed around the left anterior descending artery (LAD). The mouse chest was kept open for approximately 45 min. We chose to study an open-chest I/R SHAM because this is the reference surgery for the most common surgical procedure used to study cardiac inflammation. Mice were sacrificed 5 days after the procedure and the hearts were removed and used in RNAseq experiments.
2020-10-04 | GSE120867 | GEO