Specific Inflammatory Stimuli Lead to Distinct Platelet Responses in mice and Humans
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE68835 | GEO | 2016/05/13
SECONDARY ACCESSION(S): PRJNA283871
REPOSITORIES: GEO
Similar Datasets
Project description:Different inflammatory stimuli contribute to the formation of atherosclerosis. It is hypothesized that although the end result is the same - plaque formation in arterial vessels - the pathogenesis is dependent on the etiology. In particular, platelets will respond differently depending on the inflammatory stimuli and timepoint. Using a microarray and platelet inflammatory function studies, we identified the transcriptional and functional changes that occur early and late with different inflammatory stimuli. ApoE-/- C57BL/6 mice were left untreated (control) or administered oral P. gingivalis (Pg) or intranasal C. pneumoniae (Cp) for 3 weeks, and sacrificed either 1 day (early timepoint) or 9 weeks (late timepoint) after this 3-week period. A separate group of animals was fed a Western Diet (WD) for 9 weeks and then sacrificed. Whole blood samples were collected from each animal into citrate solution and serially centrifuged to produce a pure platelet population. RNA was extracted and pooled from each experimental group and hybridized to Affymetrix Mouse Gene 1.0 ST microarrays.
2016-05-13 | E-GEOD-68835 | biostudies-arrayexpress
Project description:IntroductionDiverse and multi-factorial processes contribute to the progression of cardiovascular disease. These processes affect cells involved in the development of this disease in varying ways, ultimately leading to atherothrombosis. The goal of our study was to compare the differential effects of specific stimuli--two bacterial infections and a Western diet--on platelet responses in ApoE-/- mice, specifically examining inflammatory function and gene expression. Results from murine studies were verified using platelets from participants of the Framingham Heart Study (FHS; n = 1819 participants).MethodsBlood and spleen samples were collected at weeks 1 and 9 from ApoE-/- mice infected with Porphyromonas gingivalis or Chlamydia pneumoniae and from mice fed a Western diet for 9 weeks. Transcripts based on data from a Western diet in ApoE-/- mice were measured in platelet samples from FHS using high throughput qRT-PCR.ResultsAt week 1, both bacterial infections increased circulating platelet-neutrophil aggregates. At week 9, these cells individually localized to the spleen, while Western diet resulted in increased platelet-neutrophil aggregates in the spleen only. Microarray analysis of platelet RNA from infected or Western diet-fed mice at week 1 and 9 showed differential profiles. Genes, such as Serpina1a, Ttr, Fgg, Rpl21, and Alb, were uniquely affected by infection and diet. Results were reinforced in platelets obtained from participants of the FHS.ConclusionUsing both human studies and animal models, results demonstrate that variable sources of inflammatory stimuli have the ability to influence the platelet phenotype in distinct ways, indicative of the diverse function of platelets in thrombosis, hemostasis, and immunity.
| S-EPMC4493099 | biostudies-literature
Project description:Relationships between platelet mitochondrial oxygen consumption rates (mOCR) and metabolites in platelets as measured by quantitative 1H-NMR metabolomics. Samples collected in ED at a single timepoint. WB and platelets isolated from the same blood samples. Comparison of mitochondrial function and metabolomics in patients with sepsis and non-sepsis ED patients
2019-12-13 | ST001294 | MetabolomicsWorkbench
Project description:Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. The aim of this study was to investigate whether differences in miRNA expression levels in platelets can be found (i) between patients with premature CAD and healthy controls and (ii) within healthy controls after and before aspirin and statin administration.
2015-06-22 | GSE59421 | GEO
Project description:Acute myocardial infarction (AMI) is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis and progression of both atherosclerosis and thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors and maintain it unchanged during their life span, gene expression (GE) profiling at the time of an AMI provides information concerning the platelet GE preceding the coronary event. In ST-segment elevation myocardial infarction (STEMI), a gene-by-gene analysis of the platelet GE identified five differentially expressed genes (DEGs): FKBP5, S100P, SAMSN1, CLEC4E and S100A12. The logistic regression model used to combine the GE in a STEMI vs healthy donors score showed an AUC of 0.95. The same five DEGs were externally validated using platelet GE data from patients with coronary atherosclerosis but without thrombosis. Early signals of an imminent AMI are likely to be found by platelet GE profiling before the infarction occurs.
2019-12-31 | GSE109048 | GEO
Project description:Platelet activation is the key event triggering thrombus formation in physiological and pathological conditions, such as acute coronary syndromes. Current therapies using antiaggregants still fail to prevent thrombotic coronary events in a significant number of patients, indicating that the mechanisms modulating platelet response during activation need to be clarified. The evidence that platelets are capable of de novo protein synthesis in response to stimuli raised the issue of how the activity of megakaryocyte-derived mRNAs is regulated in these anucleate cell fragments. We applied a combined multi-omics approach to investigate this phenomenon in platelets from healthy donors activated in vitro with Collagen or Thrombin Receptor Activating Peptide. Combining HiRIEF LC-MS to transcriptome analysis by RNA-Seq allowed platelet proteome characterization at deep coverage, revealing a significant effect of either stimulus on proteome composition. In silico intron retention analysis was then applied to search for splicing events induced by platelet activation, coupled to unbiased proteogenomics, to correlate intron retention in resting platelets to intron removal by RNA splicing during activation. This allowed identification of a set of transcripts, specifically involved in platelet shape changes, showing reduced intron retention and high peptide representation at exon-exon junctions in activated vs resting platelets. These results indicate that RNA splicing events takes place in platelets during activation and that pre-mRNA maturation of specific transcripts is part of the activation cascade and could therefore provide novel molecular markers of platelet activation status in acute coronary syndromes and other pathological conditions.
2018-01-15 | E-MTAB-6148 | biostudies-arrayexpress
Project description:Tumor-educated platelets (TEPs) are a potential method of liquid biopsy for the diagnosis and monitoring of cancer. However, the mechanism underlying tumor education of platelets is not known, and transcripts associated with TEPs are often not tumor-associated transcripts. We demonstrate that direct tumor transfer of transcripts to circulating platelets is an unlikely source of the TEP signal. We use CDSeq, a latent Dirichlet allocation algorithm, to deconvolute the TEP signal in blood samples from patients with glioblastoma. We demonstrate that a significant proportion of transcripts in the platelet transcriptome are derived from non-platelet cells, and the use of this algorithm allows the removal of contaminant transcripts. Furthermore, we used the results of this algorithm to demonstrate that TEPs represent a subset of more activated platelets, which also contain transcripts normally associated with non-platelet inflammatory cells, suggesting that these inflammatory cells, possibly in the tumor microenvironment, transfer transcripts to platelets that are then found in circulation. Our analysis suggests a useful and efficient method of processing TEP transcriptomic data to enable the isolation of a unique TEP signal associated with specific tumors.
2024-10-16 | GSE271073 | GEO
Project description:Tumor-educated platelets (TEPs) are a potential method of liquid biopsy for the diagnosis and monitoring of cancer. However, the mechanism underlying tumor education of platelets is not known, and transcripts associated with TEPs are often not tumor-associated transcripts. We demonstrate that direct tumor transfer of transcripts to circulating platelets is an unlikely source of the TEP signal. We use CDSeq, a latent Dirichlet allocation algorithm, to deconvolute the TEP signal in blood samples from patients with glioblastoma. We demonstrate that a significant proportion of transcripts in the platelet transcriptome are derived from non-platelet cells, and the use of this algorithm allows the removal of contaminant transcripts. Furthermore, we used the results of this algorithm to demonstrate that TEPs represent a subset of more activated platelets, which also contain transcripts normally associated with non-platelet inflammatory cells, suggesting that these inflammatory cells, possibly in the tumor microenvironment, transfer transcripts to platelets that are then found in circulation. Our analysis suggests a useful and efficient method of processing TEP transcriptomic data to enable the isolation of a unique TEP signal associated with specific tumors.
2024-10-16 | GSE271072 | GEO
Project description:Aging involves morphological and functional changes across different organs, but how these changes are linked among the different organs remains to be elucidated. Here, we uncover a central role of platelets in sys temic aging. In aged mice, the levels of platelet secreted pro inflammatory factors (PSPF) increased greatly in the serum and platelets, leading to a diffuse increase of platelet infiltration in brain, liver, lung, kidney, and aortic root. The RNA binding protein HuR/ELAVL1, a major regulator of R NA metabolism, promoted the production of PSPF in platelets. Platelet specific deletion of HuR reduced the expression of PSPF in platelets, alleviated platelet infiltration in brain, liver, lung, kidney, and aortic root, and delayed systemic aging. Our findings highlight a role of platelets in coordinating aging traits across organs.
2024-11-16 | GSE281572 | GEO
Project description:Abstract. The role of platelets in hemostasis and thrombosis is clearly established; however, the mechanisms by which platelets mediate inflammatory and immune pathways are less well understood. Platelets interact and modulate the function of blood and vascular cells by releasing bioactive molecules. Although the platelet is anucleate, it contains transcripts that may mirror disease. Platelet mRNA is only associated with low-level protein translation, however, platelets have a unique membrane structure allowing for the passage of small molecules, leading to the possibility that its’ cytoplasmic RNA may be passed to nucleated cells. To examine this question, platelet-like particles with labeled RNA were co-cultured with vascular cells. Co-culture of platelet-like particles with activated THP-1, monocytic, and endothelial cells led to visual and functional RNA transfer. Post-transfer microarray gene expression analysis of THP-1 cells showed an increase in HBG1/HBG2 and HBA1/HBA2 expression which was directly related to the transfer. Infusion of wild-type platelets into a TLR2 deficient mouse model established in vivo confirmation of select platelet RNA transfer to leukocytes. By specifically transferring green fluorescent protein, it was also observed that external RNA was functional in the recipient cells. The observation that platelets possess the capacity to transfer cytosolic RNA suggests a new function for platelets in the regulation of vascular homeostasis. THP-1, treated with Pam3CSK4, were co-cultured with platelet-like particles for 12 hours and 24 hours then collected and processed for RNA isolation. We also included as control THP-1 untreated and THP-1 treated with Pam3CSK4. A total of 4 samples were analyzed by microarray for gene expression.
2012-05-17 | E-GEOD-38027 | biostudies-arrayexpress