Differential gene responses three days following infarction in the fetal and adolescent sheep heart
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PROVIDER: PRJNA603845 | ENA |
REPOSITORIES: ENA
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Project description:Background: There are critical molecular mechanisms that can be activated to induce myocardial repair and in humans this is most efficient during fetal development. The timing of heart development in relation to birth and the size/electrophysiology of the heart are similar in humans and sheep, providing a model to investigate the repair capacity of the mammalian heart and how this can be applied to adult heart repair. Methods: Myocardial infarction was induced by ligation of the left anterior descending coronary artery in fetal (105d gestation when cardiomyocytes are proliferative) and adolescent sheep (6 months of age when all cardiomyocytes have switched to an adult phenotype). An ovine gene microarray was used to compare gene expression in sham and infarcted (remote, border and infarct areas) cardiac tissue from fetal and adolescent hearts. Results: The gene response to myocardial infarction was less pronounced in fetal compared to adolescent sheep hearts and there were unique gene responses at each age. There were also region-specific changes in gene expression between each age, in the infarct tissue, tissue bordering the infarct, and tissue remote from the infarction. In total, there were 880 genes that responded to MI uniquely in the adolescent samples compared with 170 genes in the fetal response, as well as 742 overlap genes that showed concordant direction of change responses to infarction at both ages. Conclusions: In response to myocardial infarction, there were specific changes in genes within pathways of mitochondrial oxidation, muscle contraction, and haematopoietic cell lineages, suggesting that the control of energy utilisation and immune function are critical for effective heart repair. The more restricted gene response in the fetus may be an important factor in its enhanced capacity for cardiac repair.
2020-01-30 | GSE144509 | GEO
Project description:There are critical molecular mechanisms that can be activated to induce myocardial repair, and in humans this is most efficient during fetal development. The timing of heart development in relation to birth and the size/electrophysiology of the heart are similar in humans and sheep, providing a model to investigate the repair capacity of the mammalian heart and how this can be applied to adult heart repair. Myocardial infarction was induced by ligation of the left anterior descending coronary artery in fetal (105 days gestation when cardiomyocytes are proliferative) and adolescent sheep (6 mo of age when all cardiomyocytes have switched to an adult phenotype). An ovine gene microarray was used to compare gene expression in sham and infarcted (remote, border and infarct areas) cardiac tissue from fetal and adolescent hearts. The gene response to myocardial infarction was less pronounced in fetal compared with adolescent sheep hearts and there were unique gene responses at each age. There were also region-specific changes in gene expression between each age, in the infarct tissue, tissue bordering the infarct, and tissue remote from the infarction. In total, there were 880 genes that responded to MI uniquely in the adolescent samples compared with 170 genes in the fetal response, as well as 742 overlap genes that showed concordant direction of change responses to infarction at both ages. In response to myocardial infarction, there were specific changes in genes within pathways of mitochondrial oxidation, muscle contraction, and hematopoietic cell lineages, suggesting that the control of energy utilization and immune function are critical for effective heart repair. The more restricted gene response in the fetus may be an important factor in its enhanced capacity for cardiac repair.
| S-EPMC7099410 | biostudies-literature
Project description:Expression data from mouse heart three days after myocardial infarction
| PRJNA664127 | ENA
Project description:Identification of the genes whose expresion levels are changed by the operation of myocardial infarction in C57BL/6J mice
2022-12-19 | GSE158157 | GEO
Project description:To elucidate the impact of androgen exposure in fetal life on adolescent sheep, fetuses were exposed to either a vehicle control or testosterone propionate. Sheep were then reared to adolescence, and RNA was extracted from the liver to assess the impact of hormone exposure during fetal development.
2019-12-31 | E-MTAB-8032 | biostudies-arrayexpress
Project description:long non coding RNA expression in post myocardial infarction 3 days and 14 days
| PRJNA678292 | ENA
Project description:This experiment compared gene expression in the duodenum of [1] weaned genetically resistant sheep and weaned genetically susceptible sheep (84 days old) [2] genetically resistant sheep and genetically susceptible sheep that have been naturally challenged once with nematodes (175 days old) and [3] genetically resistant sheep and genetically susceptible sheep that have been naturally challenged twice with nematodes (276 days old). Keywords: resistant v susceptible
2006-09-06 | GSE5492 | GEO
Project description:AimsAnimal models have been used to show that there are critical molecular mechanisms that can be activated to induce myocardial repair at specific times in development. For example, specific miRNAs are critical for regulating the response to myocardial infarction (MI) and improving the response to injury. Manipulating these miRNAs in small animal models provides beneficial effects post-MI; however it is not known if these miRNAs are regulated similarly in large mammals. Studying a large animal where the timing of heart development in relation to birth is similar to humans may provide insights to better understand the capacity to repair a developing mammalian heart and its application to the adult heart.MethodsWe used a sheep model of MI that included permanent ligation of the left anterior descending (LAD) coronary artery. Surgery was performed on fetuses (at 105 days gestation when all cardiomyocytes are mononucleated and proliferative) and adolescent sheep (at 6 months of age when all cardiomyocytes contribute to heart growth by hypertrophy). A microarray was utilized to determine the expression of known miRNAs within the damaged and undamaged tissue regions in fetal and adolescent hearts after MI.Results73 miRNAs were up-regulated and 58 miRNAs were down-regulated significantly within the fetal infarct compared to remote cardiac samples. From adolescent hearts 69 non-redundant miRNAs were up-regulated and 63 miRNAs were down-regulated significantly in the infarct area compared to remote samples. Opposite differential expression profiles of 10 miRNAs within tissue regions (Infarct area, Border zone and Remote area of the left ventricle) occurred between the fetuses and adolescent sheep. These included miR-558 and miR-1538, which when suppressed using LNA anti-miRNAs in cell culture, increased cardiomyoblast proliferation.ConclusionThere were significant differences in miRNA responses in fetal and adolescent sheep hearts following a MI, suggesting that the modulation of novel miRNA expression may have therapeutic potential, by promoting proliferation or repair in a damaged heart.
| S-EPMC7298149 | biostudies-literature
Project description:microRNAs control cardiac remodeling post myocardial infarction, though the cellular and molecular mechanisms remain unclear. We used microarrays to examine microRNA profiles in mice hearts 21 days after ligation of left anterior descending coronary artery (LAD) versus sham control.
2017-02-12 | GSE74135 | GEO
Project description:To explore the key lncRNAs involved in regulating essential pathophysiological processes of the adult heart, we performed microarray-based transcriptome profiling on mouse hearts 3 days and 14 days after myocardial infarction (MI) or sham surgery. Microarray analysis revealed a total of 7,339 differentially expressed transcripts in MI 3 days hearts compared to sham controls (FC≥2, p<0.05). Kyoto Encyclopedia of Genes and Genomes (KEGG) or Gene Ontology (GO) pathway analyses revealed that oxidative phosphorylation, ECM-receptor interaction, cell proliferation, and inflammatory responses were among the top dysregulated genes in MI hearts. Interestingly, 209 lncRNAs are upregulated and 543 lncRNAs are downregulated in MI 3 days hearts (FC≥2, p<0.05). Among these lncRNA transcripts, we found that 8 lncRNAs are mostly upregulated and 6 lncRNAs mostly downregulated (FC≥2, p<0.05), whereas the expression level of the AK048087 transcript was increased by 25 fold and lncRNA AK034241 appears to be the most downregulated lncRNA.
2020-11-14 | GSE161427 | GEO