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Platelet hyperreactivity project

ABSTRACT: The aim of this study is to identify candidate genes modulating platelet reactivity in aspirin-treated cardiovascular patients using an integrative network-based approach. Platelet reactivity was assessed in 110 cardiovascular patients treated with aspirin 100mg/d by aggregometry using several agonists. Patients with extreme high or low PR were selected for further analysis. Data derived from quantitative proteomic of platelets and platelet sub-cellular fractions, as well as from transcriptomic analysis were integrated with a network biology approach.

OTHER RELATED OMICS DATASETS IN: PXD001861

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Pierre Fontana

PROVIDER: MSV000083572 | MassIVE | Thu Mar 14 13:06:00 GMT 2019

SECONDARY ACCESSION(S): PXD001861

REPOSITORIES: MassIVE

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New molecular insights into modulation of platelet reactivity in aspirin-treated patients using a network-based approach.

Zufferey Anne A Ibberson Mark M Reny Jean-Luc JL Nolli Séverine S Schvartz Domitille D Docquier Mylène M Xenarios Ioannis I Sanchez Jean-Charles JC Fontana Pierre P

Human genetics 20160216 4

Platelet reactivity (PR) is variable between individuals and modulates clinical outcome in cardiovascular (CV) patients treated with antiplatelet drugs. Although several data point to a genetic control of platelet reactivity, the genes contributing to the modulation of this phenotype are not clearly identified. Integration of data derived from high-throughput technologies may yield novel insights into the molecular mechanisms that govern platelet reactivity. The aim of this study is to identify ...[more]

PMID: 26883867

Similar Datasets

platelet hyperreactivity project

Project description:The aim of this study is to identify candidate genes modulating platelet reactivity in aspirin-treated cardiovascular patients using an integrative network-based approach. Platelet reactivity was assessed in 110 cardiovascular patients treated with aspirin 100mg/d by aggregometry using several agonists. Patients with extreme high or low PR were selected for further analysis. Data derived from quantitative proteomic of platelets and platelet sub-cellular fractions, as well as from transcriptomic analysis were integrated with a network biology approach.

2016-02-22 | PXD001861 | Pride

New molecular insights into modulation of platelet reactivity in aspirin-treated patients using a network-based approach [Affymetrix]

Project description:Platelet reactivity (PR) in cardiovascular (CV) patients is variable between individuals and modulates clinical outcome. However, the determinants of platelet reactivity are largely unknown. Integration of data derived from high-throughput omics technologies may yield novel insights into the molecular mechanisms that govern platelet reactivity. The aim of this study was to identify candidate genes modulating platelet reactivity in aspirin-treated cardiovascular patients PR was assessed in 110 CV patients treated with aspirin 100mg/d by aggregometry using several agonists. 12 CV patients with extreme high or low PR were selected for transcriptomics, proteomics and miRNA analysis. 2 extreme patient groups, 6 samples per group

2016-02-18 | E-GEOD-66426 | biostudies-arrayexpress

New molecular insights into modulation of platelet reactivity in aspirin-treated patients using a network-based approach [NanoString]

2016-02-18 | E-GEOD-66427 | biostudies-arrayexpress

New molecular insights into modulation of platelet reactivity in aspirin-treated patients using a network-based approach [NanoString]

2016-02-18 | GSE66427 | GEO

New molecular insights into modulation of platelet reactivity in aspirin-treated patients using a network-based approach [Affymetrix]

2016-02-18 | GSE66426 | GEO

Platelet microRNA expression profiles of acute coronary syndrome patients with high and low platelet reactivity

Project description:To explore the diverse platelet microRNA (miRNA) expression between high platelet reactivity (HPR) and low platelet reactivity (LPR) patients with acute coronary syndromes (ACS), we enrolled a cohort of ACS patients and performed miRNA expression profiling of platelets from four HPR and four LPR patients using human miRNA microarray system. VerifyNow P2Y12 assay was applied to indentify HPR and LPR. Venous blood was drawn from the patients and was centrifuged to prepare platelets. Among the candidate differentially expressed miRNAs, miR-15b expression was further confirmed to be lower in platelets of 22 HPR patients than 17 LPR by quantitative reverse-transcription polymerase chain reaction (RT-qPCR). We enrolled a consecutive cohort of 290 ACS patients and assessed the platelet reactivity using VerifyNow P2Y12 assay. In this study, HPR was defined as M-bM-^IM-%300 platelet reactivity unit (PRU) while LPR <170 PRU. miRNA microarray analysis was performed in platelets of four HPR and four LPR patients with ACS.

2014-07-17 | E-GEOD-59488 | biostudies-arrayexpress

Platelet microRNA expression profiles of acute coronary syndrome patients with high and low platelet reactivity

2014-07-17 | GSE59488 | GEO

Platelet microRNA-mRNA Co-Expression Profiles Correlate with Platelet Reactivity

Project description:MicroRNAs (miRNAs) regulate cell physiology by altering protein expression, but the biology of platelet miRNAs is largely unexplored. We tested whether platelet miRNA levels were associated with platelet reactivity by genome-wide profiling using platelet RNA from 19 healthy subjects. We found that human platelets express 284 miRNAs. Unsupervised hierarchical clustering of miRNA profiles resulted in 2 groups of subjects that appeared to cluster by platelet aggregation phenotypes. Seventy-four miRNAs were differentially expressed (DE) between subjects grouped according to platelet aggregation to epinephrine, a subset of which predicted the platelet reactivity response. Using whole genome mRNA expression data on these same subjects, we computationally generated a high-priority list of miRNA-mRNA pairs in which the DE platelet miRNAs had binding sites in 3'UTRs of DE mRNAs, and the levels were negatively correlated. Three miRNA-mRNA pairs (miR-200b:PRKAR2B, miR-495:KLHL5 and miR-107:CLOCK) were selected from this list and all 3 miRNAs knocked down protein expression from the target mRNA. Reduced activation from platelets lacking PRKAR2B supported these findings. In summary, (1) platelet miRNAs are able to repress expression of platelet proteins, (2) miRNA profiles are associated with and may predict platelet reactivity, and (3) bioinformatic approaches can successfully identify functional miRNAs in platelets. Total RNA from the platelets of 19 donors was harvested and labeled with Hy3. Reference RNA (a pool of all samples) was labeled with Hy5. This submission represents the miRNA expression component of the study.

2011-09-26 | E-GEOD-27917 | biostudies-arrayexpress

Platelet Reactivity ExpreSsion Score Predicts Cardiovascular Risk

Project description:Platelets are key mediators of atherothrombosis; yet, limited tools exist to identify individuals with a hyperreactive platelet phenotype. Here we derive and validate a Platelet Reactivity ExpreSsion Score (PRESS) integrating platelet aggregation responses and RNA sequencing in multiple cohorts. PRESS performs well in identifying a hyperreactive phenotype in patients with cardiovascular disease (AUC [cross-validation] 0.81, 95% CI 0.68 to 0.94), with similar discrimination in an independent cohort of healthy participants (AUC [validation] 0.77, 95% CI 0.75 to 0.79); accuracy 80%, sensitivity 71%, and specificity 86%. Next, we validate PRESS in multiple cohorts of patients with platelet RNASeq available. Following multivariable adjustment, PRESS was significantly higher in MI (β=1.8, p=0.02), and individuals with a score above the median more frequently develop a future cardiovascular event (adjusted HR 1.90, CI 1.07 to 3.36), p=0.027). Altogether, we provide strong evidence that PRESS is a robust prognostic marker, which could have an essential role in facilitating a personalized approach to cardiovascular risk management.

2024-06-30 | GSE232027 | GEO

Platelet microRNA-mRNA Co-Expression Profiles Correlate with Platelet Reactivity

2011-09-27 | GSE27917 | GEO