Next Generation Sequencing of Asymptomatic and Symptomatic Carotid Atherosclerotic Plaques
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA816103 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18325366.fastq.gz | Fastqsanger.gz | |||
| SRR18325367.fastq.gz | Fastqsanger.gz | |||
| SRR18325368.fastq.gz | Fastqsanger.gz | |||
| SRR18325369.fastq.gz | Fastqsanger.gz | |||
| SRR18325370.fastq.gz | Fastqsanger.gz |
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Project description:Atherosclerotic plaques are composed by different cell populations that interact one with each other in a complex and heterogeneous environment. Here we report a MALDI mass spectrometry imaging investigation of the lipid profile of specific plaque regions, to discriminate between symptomatic and asymptomatic atheromas. Regions were defined by histologic staining and immunofluorescence of consecutive tissue sections.
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Project description:In order to identify potential new biomarkers of atherosclerotic plaque composition we performed a large scale analysis of gene expression patterns in human atherosclerotic lesions. Whole genome expression analysis of 101 peripheral plaques identified a robust gene signature (1514 genes) dominated by inflammatory processes, and cholesterol metabolism and storage genes. Specific pathways enriched in this signature included activation of the Toll-like receptor signaling pathway, T-cell activation, cholesterol efflux, oxidative stress response, inflammatory cytokine production, vasoconstriction and lysosomal activity. Analysis of gene expression in plaque micro-dissected material revealed that the signature is strongly up-regulated in macrophage-rich regions and down-regulated in regions with high smooth muscle cell content. A smaller qPCR biomarker panel and inflammatory composite score (ICS) were developed to facilitate clinical translation of discoveries from gene expression profiling. We found that ICS correlates with histological features related to plaque vulnerability. In addition, ICS is able to separate groups of plaques obtained from symptomatic and asymptomatic patients undergoing carotid endarerectomy. In summary, we identified a robust mRNA biomarker panel associated with histo-pathological as well as clinical hallmarks of vulnerable atherosclerotic plaque. This panel may be used as a diagnostic and prognostic tool in clinical setting to evaluate novel anti-atherosclerotic therapies. Total RNA from peripheral plaque (n=101) profiled in the Merck/Agilent 44k v1.1 against a reference pool of total RNA from 7 carotid plaques.
2011-09-30 | E-GEOD-23304 | biostudies-arrayexpress
Project description:In order to identify potential new biomarkers of atherosclerotic plaque composition we performed a large scale analysis of gene expression patterns in human atherosclerotic lesions. Whole genome expression analysis of 101 peripheral plaques identified a robust gene signature (1514 genes) dominated by inflammatory processes, and cholesterol metabolism and storage genes. Specific pathways enriched in this signature included activation of the Toll-like receptor signaling pathway, T-cell activation, cholesterol efflux, oxidative stress response, inflammatory cytokine production, vasoconstriction and lysosomal activity. Analysis of gene expression in plaque micro-dissected material revealed that the signature is strongly up-regulated in macrophage-rich regions and down-regulated in regions with high smooth muscle cell content. A smaller qPCR biomarker panel and inflammatory composite score (ICS) were developed to facilitate clinical translation of discoveries from gene expression profiling. We found that ICS correlates with histological features related to plaque vulnerability. In addition, ICS is able to separate groups of plaques obtained from symptomatic and asymptomatic patients undergoing carotid endarerectomy. In summary, we identified a robust mRNA biomarker panel associated with histo-pathological as well as clinical hallmarks of vulnerable atherosclerotic plaque. This panel may be used as a diagnostic and prognostic tool in clinical setting to evaluate novel anti-atherosclerotic therapies. 6 human carotid plaques were sectioned in 1 mm thick slices. Alternative slices were used for gene expression profiling in Affymetrix/Merck custom 1.0 arrays (GPL10687), or for immunohistochemistry studies (CD68, Actin)
2011-09-30 | E-GEOD-24495 | biostudies-arrayexpress
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Project description:Recent findings have challenged the prevailing histology- or imaging-based definition of the “vulnerable plaque”. To investigate molecular characteristics associated with “clinical instability” of atherosclerosis, we performed a proteomics comparison of the vascular extracellular matrix and associated molecules in human carotid endarterectomy specimens from symptomatic versus asymptomatic patients. The proteomics data were integrated with gene expression profiling and an analysis of protein secretion by lipid-loaded human vascular smooth muscle cells. The molecular signature of plaques from symptomatic patients identified by proteomics and at least one of the other two approaches comprised matrix metalloproteinase-9, chitinase-3-like protein 1, S100A8/S100A9, cathepsin B, fibronectin and galectin-3-binding protein. These biomarker candidates were measured in 685 subjects of the Bruneck Study and found to significantly predict the progression to advanced atherosclerosis (as assessed by repeated carotid ultrasound) and the incidence of cardiovascular disease over a 10-year follow-up period, highlighting the strength of tissue-based proteomics for biomarker discovery.
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Project description:In order to identify potential new biomarkers of atherosclerotic plaque composition we performed a large scale analysis of gene expression patterns in human atherosclerotic lesions. Whole genome expression analysis of 101 peripheral plaques identified a robust gene signature (1514 genes) dominated by inflammatory processes, and cholesterol metabolism and storage genes. Specific pathways enriched in this signature included activation of the Toll-like receptor signaling pathway, T-cell activation, cholesterol efflux, oxidative stress response, inflammatory cytokine production, vasoconstriction and lysosomal activity. Analysis of gene expression in plaque micro-dissected material revealed that the signature is strongly up-regulated in macrophage-rich regions and down-regulated in regions with high smooth muscle cell content. A smaller qPCR biomarker panel and inflammatory composite score (ICS) were developed to facilitate clinical translation of discoveries from gene expression profiling. We found that ICS correlates with histological features related to plaque vulnerability. In addition, ICS is able to separate groups of plaques obtained from symptomatic and asymptomatic patients undergoing carotid endarerectomy. In summary, we identified a robust mRNA biomarker panel associated with histo-pathological as well as clinical hallmarks of vulnerable atherosclerotic plaque. This panel may be used as a diagnostic and prognostic tool in clinical setting to evaluate novel anti-atherosclerotic therapies. 290 human peripheral plaques were excised using the FoxHollow silverhawk catheter and stored in RNAlater. RNA was extracted, amplified and hybridized to Affymetrix/Merck custom 1.0 arrays (GPL10687).
2011-09-30 | E-GEOD-24702 | biostudies-arrayexpress
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