Characterization of the platelet transcriptome by RNA sequencing in patients with acute myocardial infarction.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE65705 | GEO | 2015/09/15
SECONDARY ACCESSION(S): PRJNA274751
REPOSITORIES: GEO
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Project description:Recent technological advances have made transcriptome sequencing (RNA-seq) possible in cells with low RNA copy number including platelets. Resulting studies have used RNA-seq in platelets isolated from healthy individuals to characterize the platelet transcriptome. However, platelets, possibly through gene expression changes, contribute to the etiology of and response to cardiovascular disease and events. To address this, we performed the largest human platelet RNA-seq analysis to date in 34 platelet samples: 16 ST-segment elevation myocardial infarction (STEMI), 16 non-STEMI (NSTEMI), and 2 controls. RNA-seq of platelet samples from 34 individuals: 16 with ST-elevation myocardial infarction (STEMI), 16 with non-STEMI, and 2 non-myocardial infarction controls
2015-09-15 | E-GEOD-65705 | biostudies-arrayexpress
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:Platelets are central to the pathophysiology of myocardial infarction (MI). How the platelet proteome is altered during MI is unknown. We sought to describe changes in the platelet proteome at the time of MI and identify potential mechanisms. Platelets from patients experiencing ST-elevation myocardial infarction (STEMI) before and 3 days after treatment (n= 30), and a matched cohort of patients with severe stable coronary artery disease (CAD) prior to and 3 days after coronary artery bypass grafting (CABG, n=25) underwent quantitative proteomic analysis. Elevations of the alarmins S100A8 and S100A9 were detected at the time of STEMI compared with stable CAD (S100A8, FC = 2.00, FDR = 0.05; S100A9, FC = 2.28, FDR = 0.005). During STEMI, S100A8 mRNA and protein levels were correlated in platelets (R = 0.46, p = 0.012). To determine if protein synthesis occurs, activated platelets were incubated with 13C-labelled amino acids for 24 hours and analyzed by mass spectrometry. No incorporation was detected, consistent with the notion that protein synthesis in platelets is not a major contributor to the platelet proteome. Platelet abundance of S100A8 and A9 was strongly correlated with neutrophil abundance at the time of STEMI. When isolated platelets and neutrophils were co-incubated under quiescent and TRAP-6 activated conditions, release of S100A8 from neutrophils resulted in uptake of S100A8 by platelets. Leukocyte-to-platelet protein transfer, rather than protein synthesis, may occur in a thromboinflammatory environment such as STEMI, representing a potential new contributor in the innate immune pathogenesis of STEMI.
2023-11-15 | PXD024159 | Pride
Project description:Platelets are central to the pathophysiology of myocardial infarction (MI). How the platelet proteome is altered during MI is unknown. We sought to describe changes in the platelet proteome at the time of MI and identify potential mechanisms. Platelets from patients experiencing ST-elevation myocardial infarction (STEMI) before and 3 days after treatment (n= 30), and a matched cohort of patients with severe stable coronary artery disease(CAD) prior to and 3 days after coronary artery bypass grafting (CABG, n=25) underwent quantitative proteomic analysis. Elevations of the alarmins S100A8 and S100A9 were detected at the time of STEMI compared with stable CAD (S100A8, FC = 2.00, FDR = 0.05; S100A9, FC = 2.28, FDR = 0.005). During STEMI, S100A8 mRNA and protein levels were correlated in platelets (R = 0.46, p = 0.012). To determine if protein synthesis occurs, activated platelets were incubated with 13C-labelled amino acids for 24 hours and analyzed by mass spectrometry. No incorporation was detected, consistent with the notion that protein synthesis in platelets is not a major contributor to the platelet proteome. Platelet abundance of S100A8 and A9 was strongly correlated with neutrophil abundance at the time of STEMI. When isolated platelets and neutrophils were co-incubated under quiescent and TRAP-6 activated conditions, release of S100A8 from neutrophils resulted in uptake of S100A8 by platelets. Leukocyte-to-platelet protein transfer, rather than protein synthesis, may occur in a thromboinflammatory environment such as STEMI, representing a potential new contributor in the innate immune pathogenesis of STEMI.
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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
Project description:Upon activation, platelets release a host of soluble and vesicular signals, collectively termed the ‘platelet releasate’ (PR). The contents of this PR play a significant role in haemostasis, inflammation, and pathologic sequelae. Despite this, proteomic studies investigating the PR in coronary artery disease have not been performed. We undertook a comparative label-free quantitative (LFQ) proteomic profiling of the 1U/ml thrombin-induced PR from 13 acute coronary syndrome (ACS-STEMI) versus 14 stable angina pectoris patients using a tandem mass spectrometry approach. We identified differentially released platet proteins including tetranectin (CLEC3B), protein disulfide-isomerase-A3 (PDIA3), coagulation factor V (F5) and fibronectin (FN1). Strikingly, all 9 differential proteins were associated with the GO cellular component term ‘extracellular vesicle’ and reduced levels of EVs were detected in plasma of ACS-STEMI patients. Network analysis revealed 3 PR proteins either reduced (F5; FN1) or absent (CLEC3B) in ACS-STEMI patients, which are strongly connected to both the clotting cascade and major druggable targets on platelets. This moderated signature highlights the possible basis of platelet dysfunction in ACS-STEMI and may prove useful for non-invasive risk assessment of the progression of coronary artery disease.
2020-06-05 | PXD009356 | Pride
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.
2011-09-27 | GSE27917 | GEO
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.
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