Project description:Plasmacytoid dendritic cells (pDCs) are scarcely present in the inflamed human atherosclerotic plaque, where they are presumed to exert pro-inflammatory functions through release of type I interferons. However, the precise role of pDCs in human atherosclerosis yet remains to be established. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. We investigated the impact of human plaque pDCs on its local context, applying state of the art transcriptomics analysis on Laser Capture Microdissected fractions of human atherosclerotic plaques, distinctively enriched in pDCs, or pDCs-void.
Project description:This SuperSeries is composed of the following subset Series: GSE23303: Gene expression profiling of human atherosclerotic plaque: Laser capture microscopy of smooth muscle cells and macrophages GSE23304: Gene expression profiling of human atherosclerotic plaque: 101 peripheral plaques GSE24495: Gene expression profiling of human atherosclerotic plaque: Carotid plaque GSE24702: Gene expression profiling of human atherosclerotic plaque: 290 peripheral plaques Refer to individual Series
Project description:The aim of this study was to understand if gene expression in atherosclerotic plaque macrophages is altered by diabetes. Laser capture microdissection (LCM) was used to specifically isolate macrophage enriched regions from human carotid atherosclerotic plaque samples. RNA isolated was then sent for sequencing using the Illumina bead array system. Gene expression data revealed that 106 genes from diabetic macrophages are differentially expressed (FDR<0.2) and provide mechanistic evidence for the involvement of Runt-related transcription factor 1 (RUNX1) in the development of diabetic atherosclerosis.
Project description:Plasmacytoid dendritic cells (pDCs) are scarcely present in the inflamed human atherosclerotic plaque, where they are presumed to exert pro-inflammatory functions through release of type I interferons. However, the precise role of pDCs in human atherosclerosis yet remains to be established. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.
Project description:Transcriptional profiling of aortic sinus atherosclerotic plaque macrophages obtained by laser capture microdissection from male ApoE deficient mice infected with 5x10(5) cfu serotype 4 Streptococcus pneumoniae via intranasal instillation (n=9) as compared with mice mock infected with PBS (n=11). Mice were culled 2 weeks post infection/mock infection.
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. Laser captured smooth muscle cells and macrophages from carotid plaque sections (n=3) profiled in the Merck/Agilent 44k v1.1. The reference sample was a pool RNA from whole sections.
Project description:This study has investigated several parameters to obtain increased detection of the amyloid plaque intact protein profile, including a comparison of commonly used MALDI matrices, acid based reduction of signal suppression as well as the combination of strong acid based protein aggregate extraction from laser microdissection plaques to increase detection of proteoforms. Female APPPS1-21 transgenic mice were analyzed by MALDI Imaging with different matrices on a Ultraflextreme MALDI TOF/TOF instrument followed by data analysis in SCiLS Lab software. A combination of formic acid treatment of laser capture microdissected plaques was further utilized to expand the analysis and validation of amyloid plaques.
Project description:This study aims to identify and characterize miRNA expression inATLOs isolated by laser microdissection from human AAA biopsy samples. The aim of this study was to profile (with microarray technology) miRNAs in ATLOs (Adventitial tertiary lymphoid organs), isolated by laser capture microdissection (LCM). Smooth muscle cells (SMCs) isolated from control non-aneurysmal aortas were the control group according to which data were normalized. ATLOs were microdissected (mean 13.5mm2) from two different biopsy samples of human abdominal aortic aneurysm. An area enriched in smooth muscle cells was microdissected from two biopsy samples of non aneurysmal abdominal aortas. Each microdissected samples were analyzed independently on microarray.
