Insulin-like growth factor I reduces coronary atherosclerosis in pigs with familial hypercholesterolemia
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA909247 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22548606.fastq.gz | Fastqsanger.gz | |||
| SRR22548607.fastq.gz | Fastqsanger.gz | |||
| SRR22548608.fastq.gz | Fastqsanger.gz | |||
| SRR22548609.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:To investigate effects of IGF-1 on human-like coronary atherosclerosis we used high fat diet-fed Rapacz pigs with familial hypercholesterolemia (FH pigs). We used spatial transcriptomics (ST) analysis to identify global transcriptome changes in advanced plaque compartments and to obtain mechanistic insights into IGF-1 effects. IGF-1-injected FH pigs had 1.8-fold increase in total circulating IGF-1 levels compared to control. IGF-1 decreased relative coronary atheroma (data obtained by serial intravascular ultrasound) and lesion cross-sectional area (post-mortem histology). IGF-1 increased fibrous cap thickness, and reduced necrotic core size, macrophage content, and cell apoptosis, changes consistent with promotion of a stable plaque phenotype. ST analysis revealed that IGF-1 suppressed FOS/FOSB factors and gene expression of MMP9 and CXCL14 suggesting possible involvement of these molecules in IGF-1’s effect on atherosclerosis.
2023-12-03 | GSE220218 | GEO
Project description:Atherosclerosis is a chronic disease involving multiple biological mechanisms. A study aimed to identify changes in miRNA expression at early stages using a large swine model. 18 female pigs were studied, 9 with familial hypercholesterolemia and 9 normal controls. Plasma was collected at 3, 6, and 9 months of age. In vivo imaging and histopathology were performed to document the presence of coronary atherosclerosis. miRNA sequencing was carried out on plasma cell-free RNA. Results showed that circulating miRNA dynamics change over time during atherosclerosis development and specific DE miRNAs may be promising biomarkers for early detection of coronary atherosclerosis.
2023-11-08 | GSE242074 | GEO
Project description:Affymetrix microarray (GeneChip microRNA 4.0) profilling of circulating miRNAs. We used miRNA arrays to profile miRNAs isolated from plasma from familial hypercholesterolemia patients with (FH-W_CCS) or without (FH-WO_CCS) coronary calcium score by computed tomographic angiography
2024-03-26 | GSE178126 | GEO
Project description:Atherosclerosis is characterized by thickening of the arterial wall and is the primary cause of the coronary artery disease and cerebrovascular disease, two of the most common causes of illness and death worldwide. One of the leading risk factors for development of atherosclerosis is familial hypercholesterolemia. Familial hypercholesterolemia is an autosomal dominant disorder, which is caused by mutations mainly located in the low-density lipoprotein receptor (LDLR) gene. It is characterized by elevated levels of low-density lipoprotein cholesterol, the presence of tendon xanthomas, and premature cardiovascular disease. Aim of this study was to find atherosclerotic markers in white blood cells of patients compared to healthy controls. None of these patients exhibited symptoms of atherosclerosis by standard diagnostic methods; however, transcriptome analysis of blood RNA indicated changes in ubiquitin proteolysis and cell adhesion system as expected in initiation steps of atherosclerosis.
2008-12-18 | GSE13985 | GEO
Project description:Atherosclerosis is characterized by thickening of the arterial wall and is the primary cause of the coronary artery disease and cerebrovascular disease, two of the most common causes of illness and death worldwide. One of the leading risk factors for development of atherosclerosis is familial hypercholesterolemia. Familial hypercholesterolemia is an autosomal dominant disorder, which is caused by mutations mainly located in the low-density lipoprotein receptor (LDLR) gene. It is characterized by elevated levels of low-density lipoprotein cholesterol, the presence of tendon xanthomas, and premature cardiovascular disease. Aim of this study was to find atherosclerotic markers in white blood cells of patients compared to healthy controls. None of these patients exhibited symptoms of atherosclerosis by standard diagnostic methods; however, transcriptome analysis of blood RNA indicated changes in ubiquitin proteolysis and cell adhesion system as expected in initiation steps of atherosclerosis. Experiment Overall Design: Five patients diagnosed with Familial hypercholesterolemia and five age, sex, BMI and smoking status matched controls contributed blood from which total RNA from white blood cells was isolated. RNA samples were analyzed using Affymetrix microarrays and two groups were compared for differentially expressed genes.
2009-01-13 | E-GEOD-13985 | biostudies-arrayexpress
Project description:Atherosclerosis is the major cause of death in industrialized countries. This disease has initially been characterized as a lipid disorder, but current concepts argue for an inflammatory disease, which develops in the background of hypercholesterolemia and other risk factors. In response to initial events of atherosclerosis formation, such as LDL-deposition in the subendothelial space, monocytes and T cells interact with the vessel wall. However, little is known about the properties and the behavior of these cells in this context. Using familial hypercholesterolemia (FH) as a model we demonstrate substantial differences in the gene expression of freshly isolated human monocytes and T lymphocytes. In FH monocytes we found an increased uptake of oxidized LDL, elevated amounts of scavenger receptors and adhesion molecules, and differences in the regulation of intracellular lipoprotein metabolism compared to monocytes from healthy individuals. Furthermore, the monocyte subpopulation of CD14+/CD16+ cells is less frequent in FH but exhibits significantly higher levels of CD11c and CD29 which increases the likelihood for their transmigration through the endothelial layer. The presence of increased amounts of CD69 in T lymphocytes from FH patients suggests that these cells are more activated than control cells. Our results indicate that some important steps of atherosclerosis formation already take place in circulating blood cells which extends current atherosclerosis models to the plasma compartment. Keywords: atherosclerosis, T cells, Familial Hypercholesterolemia
2008-04-01 | GSE6088 | GEO
Project description:Circulating miRNA profile and coronary calcification in asymptomatic patients with familial hypercholesterolemia.
| PRJNA737428 | ENA
Project description:Although murine models of coronary atherosclerotic disease have been used extensively to determine mechanisms, limited new therapeutic options have emerged. Pigs with familial hypercholesterolemia (FH pigs) develop complex coronary atheromas that are almost identical to human lesions. We reported previously that insulin-like growth factor 1 (IGF-1) reduced aortic atherosclerosis and promoted features of stable plaque in a murine model. We administered human recombinant IGF-1 or saline (control) in atherosclerotic FH pigs for 6 months. IGF-1 decreased relative coronary atheroma in vivo (intravascular ultrasound) and reduced lesion cross-sectional area (postmortem histology). IGF-1 increased plaque's fibrous cap thickness, and reduced necrotic core, macrophage content, and cell apoptosis, consistent with promotion of a stable plaque phenotype. IGF-1 reduced circulating triglycerides, markers of systemic oxidative stress, and CXCL12 chemokine levels. We used spatial transcriptomics (ST) to identify global transcriptome changes in advanced plaque compartments and to obtain mechanistic insights into IGF-1 effects. ST analysis showed that IGF-1 suppressed FOS/FOSB factors and gene expression of MMP9 and CXCL14 in plaque macrophages, suggesting possible involvement of these molecules in IGF-1's effect on atherosclerosis. Thus, IGF-1 reduced coronary plaque burden and promoted features of stable plaque in a pig model, providing support for consideration of clinical trials.
| S-EPMC9990768 | biostudies-literature
Project description:Atherosclerosis is the major cause of death in industrialized countries. This disease has initially been characterized as a lipid disorder, but current concepts argue for an inflammatory disease, which develops in the background of hypercholesterolemia and other risk factors. In response to initial events of atherosclerosis formation, such as LDL-deposition in the subendothelial space, monocytes and T cells interact with the vessel wall. However, little is known about the properties and the behavior of these cells in this context. Using familial hypercholesterolemia (FH) as a model we demonstrate substantial differences in the gene expression of freshly isolated human monocytes and T lymphocytes. In FH monocytes we found an increased uptake of oxidized LDL, elevated amounts of scavenger receptors and adhesion molecules, and differences in the regulation of intracellular lipoprotein metabolism compared to monocytes from healthy individuals. Furthermore, the monocyte subpopulation of CD14+/CD16+ cells is less frequent in FH but exhibits significantly higher levels of CD11c and CD29 which increases the likelihood for their transmigration through the endothelial layer. The presence of increased amounts of CD69 in T lymphocytes from FH patients suggests that these cells are more activated than control cells. Our results indicate that some important steps of atherosclerosis formation already take place in circulating blood cells which extends current atherosclerosis models to the plasma compartment. Experiment Overall Design: 25 monocytes samples: 5 homozygous FH, 7 heterozygous FH, 13 control participants
2008-06-14 | E-GEOD-6054 | biostudies-arrayexpress
Project description:Atherosclerosis is the major cause of death in industrialized countries. This disease has initially been characterized as a lipid disorder, but current concepts argue for an inflammatory disease, which develops in the background of hypercholesterolemia and other risk factors. In response to initial events of atherosclerosis formation, such as LDL-deposition in the subendothelial space, monocytes and T cells interact with the vessel wall. However, little is known about the properties and the behavior of these cells in this context. Using familial hypercholesterolemia (FH) as a model we demonstrate substantial differences in the gene expression of freshly isolated human monocytes and T lymphocytes. In FH monocytes we found an increased uptake of oxidized LDL, elevated amounts of scavenger receptors and adhesion molecules, and differences in the regulation of intracellular lipoprotein metabolism compared to monocytes from healthy individuals. Furthermore, the monocyte subpopulation of CD14+/CD16+ cells is less frequent in FH but exhibits significantly higher levels of CD11c and CD29 which increases the likelihood for their transmigration through the endothelial layer. The presence of increased amounts of CD69 in T lymphocytes from FH patients suggests that these cells are more activated than control cells. Our results indicate that some important steps of atherosclerosis formation already take place in circulating blood cells which extends current atherosclerosis models to the plasma compartment. Experiment Overall Design: 23 T cells samples: 3 homozygous FH, 7 heterozygous FH, 13 control participants
2008-06-14 | E-GEOD-6088 | biostudies-arrayexpress