Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MicroRNA expression profile of platelets in sickle cell disease

ABSTRACT: Circulating platelets from Sickle cell disease (SCD) patients express distinct gene expression patterns that regulate function. The objective of this study is to identify a role of post-transcriptional regulation of the platelet transcriptional signaling by microRNAs. Comparison of microRNA expression in platelets from SCD patients and control subjects, from 2 cohorts-University of Pittsburgh and National Institutes of Health.

ORGANISM(S): Homo sapiens

SUBMITTER: Shilpa Jain

PROVIDER: E-GEOD-41574 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Expression of regulatory platelet microRNAs in patients with sickle cell disease.

Jain Shilpa S Kapetanaki Maria G MG Raghavachari Nalini N Woodhouse Kimberly K Yu Guoying G Barge Suchitra S Coronnello Claudia C Benos Panayiotis V PV Kato Gregory J GJ Kaminski Naftali N Gladwin Mark T MT

PloS one 20130412 4

<h4>Background</h4>Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile.<h4>Methods and findings</h4>We analyzed the expression of miRNAs isolated from ...[more]

PMID: 23593351

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Project description:In sickle cell disease, ischemia-reperfusion injury and intravascular hemolysis produce endothelial dysfunction and vasculopathy characterized by reduced nitric oxide (NO) and arginine bioavailability. Recent functional studies of platelets in patients with sickle cell disease reveal a basally activated state, suggesting that pathological platelet activation may contribute to sickle cell disease vasculopathy. Studies were therefore undertaken to examine transcriptional signaling pathways in platelets that may be dysregulated in sickle cell disease. We demonstrate and validate here the feasibility of comparative platelet transcriptome studies on clinical samples from single donors, by the application of RNA amplification followed by microarray-based analysis of 54,000 probe sets. Data mining an existing microarray database, we identified 220 highly abundant genes in platelets and a subset of 72 relatively platelet-specific genes, defined by more than 10-fold increased expression compared to the median of other cell types in the database with amplified transcripts. The highly abundant platelet transcripts found in the current study included 82% or 70% of platelet abundant genes identified in two previous gene expression studies on non-amplified mRNA from pooled or apheresis samples, respectively. On comparing the platelet gene expression profiles in 18 patients with sickle cell disease in steady state to 12 African American controls, at a 3-fold cut-off and 5% false discovery rate, we identified ~100 differentially expressed genes, including multiple genes involved in arginine metabolism and redox homeostasis. Further characterization of these pathways using real time PCR and biochemical assays revealed increased arginase II expression and activity and decreased platelet polyamine levels. These studies suggest a potential pathogenic role for platelet arginase and altered arginine and polyamine metabolism in sickle cell disease and provide a novel framework for the study of disease-specific platelet biology. Experiment Overall Design: There are 18 sickle cell samples and 12 control samples from healthy African American volunteers.

Dataset Information

MicroRNA expression profile of platelets in sickle cell disease

Publications

Expression of regulatory platelet microRNAs in patients with sickle cell disease.

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