A novel lesional transciptional signature separates atherosclerosis with and without diabetes in Yorkshire swine and humans
Ontology highlight
ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE162391 | GEO | 2021/02/01
REPOSITORIES: GEO
Similar Datasets
Project description:[Figure: see text].
| S-EPMC7990701 | biostudies-literature
Project description:A novel lesional transciptional signature separates atherosclerosis with and without diabetes in Yorkshire swine and humans
| PRJNA681802 | ENA
Project description:Despite unprecedented advances in the treatment of atherosclerotic cardiovascular diseases (CVD), it remains the leading cause of death in patients with diabetes worldwide. Lipid-laden atherosclerotic plaque development within the arterial vessel wall is initiated with endothelial cell activation, monocyte adhesion and foam cell formation. Although the current focus has been on mitigation of risk factors, the disease continues to progress, and thus newer approaches and druggable targets need to be identified that can directly inhibit the underlying pathobiology of atherosclerosis. We utilised a single cell RNA sequencing (scRNA-seq) approach to distinguish the proatherogenic transcriptional profile of aortic cells in diabetes.
2024-09-09 | GSE211216 | GEO
Project description:Circular RNAs (circRNAs) are broadly expressed in eukaryotic cells, but their role in human health and disease remains obscure. Here, we show that circular antisense non-coding RNA in the INK4 locus (circANRIL), which is transcribed at a locus of atherosclerotic cardiovascular disease on chromosome 9p21, confers athero-protection by controlling ribosomal RNA (rRNA) maturation and modulating pathways of atherogenesis. At the molecular level, circANRIL competes with precursor rRNA (pre-rRNA) for binding to pescadillo homolog 1 (PES1), an essential 60S-preribosomal assembly factor, thereby impairing exonuclease-mediated pre-rRNA processing and ribosome biogenesis. As a consequence, circANRIL induces nucleolar stress and p53 activation, resulting in the induction of apoptosis and inhibition of proliferation, which are key athero-protective cell functions within the arterial wall. Collectively, these findings identify circANRIL as a prototype of a circRNA regulating ribosome biogenesis and conferring athero-protection, thereby unveiling a therapeutic potential of certain circRNAs in human disease.
2017-03-28 | MSV000080698 | MassIVE
Project description:Adipose tissue inflammation and atherosclerosis are the main mechanisms behind type 2 diabetes and cardiovascular disease respectively, the major risks associated with the metabolic syndrome. Studies considering more than single factors behind the complexity of the metabolic syndrome are valuable to achieve a better and wider understanding of the metabolic syndrome. In this study common dysregulated pathways between adipose tissue inflammation and atherosclerosis were identified using two different bioinformatic tools to perform pathway analysis. First, we run a gene set enrichment analysis utilizing with data from two microarray experiments done with gonadal white adipose tissue and atherosclerotic aorta. Once the common dysregulated pathways between both tissues were identify, the inflammatory response and the oxidative phosphorylation pathways from the Hallmark geneset were selected to conduct a deeper checkup at the single gene level of these pathways. Second, we carried out a pathway analysis validation with the Panther™ software combining the microarray data with a published type 2 diabetes mellitus metanalysis and cardiovascular disease metanalysis which included human data. In conclusion, this study provides worthwhile data pointing out and describing several dysregulated and common pathways in adipose tissue inflammation and atherosclerotic aorta with a potential implication in the pathogenesis of type 2 diabetes and atherosclerosis.
2016-09-01 | GSE76812 | GEO
Project description:Circular RNAs (circRNAs) are broadly expressed in eukaryotic cells, but their role in human health and disease remains obscure. Here, we show that circular antisense non-coding RNA in the INK4 locus (circANRIL), which is transcribed at a locus of atherosclerotic cardiovascular disease on chromosome 9p21, confers athero-protection by controlling ribosomal RNA (rRNA) maturation and modulating pathways of atherogenesis. At the molecular level, circANRIL competes with precursor rRNA (pre-rRNA) for binding to pescadillo homolog 1 (PES1), an essential 60S-preribosomal assembly factor, thereby impairing exonuclease-mediated pre-rRNA processing and ribosome biogenesis. As a consequence, circANRIL induces nucleolar stress and p53 activation, resulting in the induction of apoptosis and inhibition of proliferation, which are key athero-protective cell functions within the arterial wall. Collectively, these findings identify circANRIL as a prototype of a circRNA regulating ribosome biogenesis and conferring athero-protection, thereby unveiling a therapeutic potential of certain circRNAs in human disease.
2016-06-10 | PXD001769 | Pride
Project description:Atherosclerosis is an inflammatory-driven disease involving complex mechanisms. Our study investigated the transcriptomic profile of swine abdominal aortic tissues with atherosclerotic lesions, identified pathways and biological processes that were enriched in DEGs, determined a set of hub genes central to atherosclerosis pathophysiology that may serve as potential therapeutic targets, and established a positive expression correlation between the top hub gene and its interconnecting genes upon in vitro manipulation. Our data showed that WMS FH exhibits immune and inflammation-related pathways. RNA-Seq result demonstrated distinct expression patterns between abdominal aortic tissue with atherosclerotic lesions (WMS FH) and lesion-free tissues (WMS normal) both at the gene and isoform levels. Ten hub genes were identified, including ITGB2, C1QA, LCP2, SPI1, CSF1R, CSF2RB, C5AR1, CTSS, MPEG1, C1QC. Moreover, manipulating the top-ranked gene (ITGB2) expression in porcine endothelial cells affected the expression of interconnecting genes.
2023-11-24 | GSE199592 | GEO
Project description:During the inflammatory response that drives atherogenesis, macrophages accumulate progressively in the expanding arterial wall. The observation that circulating monocytes give rise to lesional macrophages has reinforced the concept that monocyte infiltration dictates macrophage buildup. Recent work has indicated, however, that macrophage accumulation does not depend on monocyte recruitment in some inflammatory contexts. We therefore revisited the mechanism underlying macrophage accumulation in atherosclerosis. In murine atherosclerotic lesions, we found that macrophages turn over rapidly, after 4 weeks. Replenishment of macrophages in these experimental atheromata depends predominantly on local macrophage proliferation rather than monocyte influx. The microenvironment orchestrates macrophage proliferation through the involvement of scavenger receptor A (SR-A). Our study reveals macrophage proliferation as a key event in atherosclerosis and identifies macrophage self-renewal as a therapeutic target for cardiovascular disease.
| S-EPMC3769444 | biostudies-literature
Project description:Circular RNAs (circRNAs) are broadly expressed in eukaryotic cells, but their role in human health and disease remains obscure. Here, we show that circular antisense non-coding RNA in the INK4 locus (circANRIL), which is transcribed at a locus of atherosclerotic cardiovascular disease on chromosome 9p21, confers athero-protection by controlling ribosomal RNA (rRNA) maturation and modulating pathways of atherogenesis. At the molecular level, circANRIL competes with precursor rRNA (pre-rRNA) for binding to pescadillo homolog 1 (PES1), an essential 60S-preribosomal assembly factor, thereby impairing exonuclease-mediated pre-rRNA processing and ribosome biogenesis. As a consequence, circANRIL induces nucleolar stress and p53 activation, resulting in the induction of apoptosis and inhibition of proliferation, which are key athero-protective cell functions within the arterial wall. Collectively, these findings identify circANRIL as a prototype of a circRNA regulating ribosome biogenesis and conferring athero-protection, thereby unveiling a therapeutic potential of certain circRNAs in human disease. Analysis of transcriptome-wide expression level in HEK293 cells with stable overexpression of circular ANRIL (n=3) compared to a vector control (n=3).
2016-08-22 | E-GEOD-65392 | biostudies-arrayexpress
Project description:Adipose tissue inflammation and atherosclerosis are the main mechanisms behind type 2 diabetes and cardiovascular disease respectively, the major risks associated with the metabolic syndrome. Studies considering more than single factors behind the complexity of the metabolic syndrome are valuable to achieve a better and wider understanding of the metabolic syndrome. In this study common dysregulated pathways between adipose tissue inflammation and atherosclerosis were identified using two different bioinformatic tools to perform pathway analysis. First, we run a gene set enrichment analysis utilizing with data from two microarray experiments done with gonadal white adipose tissue and atherosclerotic aorta. Once the common dysregulated pathways between both tissues were identify, the inflammatory response and the oxidative phosphorylation pathways from the Hallmark geneset were selected to conduct a deeper checkup at the single gene level of these pathways. Second, we carried out a pathway analysis validation with the Panther⢠software combining the microarray data with a published type 2 diabetes mellitus metanalysis and cardiovascular disease metanalysis which included human data. In conclusion, this study provides worthwhile data pointing out and describing several dysregulated and common pathways in adipose tissue inflammation and atherosclerotic aorta with a potential implication in the pathogenesis of type 2 diabetes and atherosclerosis. LDLR-/- on a C57BL/6J background, purchased from Charles River Laboratories (Sulzfeld, Germany) were used. At 9 weeks of age the LDLR-/- were placed for up to 20 weeks on sucrose-enriched high-fat diet (HFSC) (with 17.5 kcal% from sucrose; (D09071704, Research Diets Inc.). Their respective controls were kept on normal chow diet (NC) for up to 20 weeks. After sacrificing the gonadal white adipose tissue (GWAT) from LDLR-/- animals on NC (Samples 22-27) or HFSC (Samples 28-33) was collected as well as the whole aortae from LDLR-/- animals on NC (Samples 13-15) or HFSC (Samples16-18). The collected tissues were immediately snap frozen in liquid nitrogen. RNA was isolated for gene expression microarray analyses at the exon level (GeneChip Mouse Exon 2.0 ST Array, Affymetrix, Santa Clara, CA, USA). To isolate RNA, the frozen tissue samples were homogenized in TRIzol® reagent (Invitrogen/Life Technologies, Carlsbad, CA, USA) and processed based on manufacturerâs instructions. Total RNA (1μg) was then used for GeneChip analysis, individual samples were used in GWAT preparation and three samples were pooled and used for aorta preparations. Terminal-labeled cDNA, hybridization to genome-wide Mouse Gene 2.0 ST Gene Chips and scanning of the arrays were carried out according to the manufactureâs indications (Affymetrix).Output primary row data was analyzed with Expression Console software (Affymetrix).
2016-09-01 | E-GEOD-76812 | biostudies-arrayexpress