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pmid:32671099
Comparative Platelet Releasate Proteomic Profiling of Acute Coronary Syndrome versus Stable Coronary Artery Disease.
Patricia B Maguire · Martin E Parsons · Paulina B Szklanna · Monika Zdanyte · Patrick Münzer · Madhumita Chatterjee · Kieran Wynne · Dominik Rath · Shane P Comer · Melanie Hayden · Fionnuala Ní Áinle · Meinrad Gawaz
Frontiers in cardiovascular medicine · 2020 doi:10.3389/fcvm.2020.00101
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Complete file
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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. Here, we undertook a comparative label-free quantitative (LFQ) proteomic profiling of the 1 U/ml thrombin-induced PR from 13 acute coronary syndrome vs. 14 stable angina pectoris patients using a tandem mass spectrometry approach. Data are available via ProteomeXchange with identifier PXD009356. 318 PR proteins were identified across both cohorts with 9 proteins found to be differentially released, including tetranectin (CLEC3B), protein disulfide-isomerase-A3 (PDIA3), coagulation factor V (F5), and fibronectin (FN1). Strikingly, these 9 differential proteins were all associated with the gene ontology cellular component term \"extracellular vesicle\" and reduced levels of EVs were detected in the corresponding plasma of ST-segment elevation myocardial infarction (STEMI) patients. Network analysis revealed 3 proteins either reduced (F5; FN1) or absent (CLEC3B) in the PR of STEMI patients that are strongly connected to both the clotting cascade and major druggable targets on platelets. This moderated proteomic signature may prove useful for non-invasive risk assessment of the progression of coronary artery disease. These data further contribute to the growing evidence-base of using the platelet releasate as a predictor of pathological state and disease severity.", "claims": [{"id": "claim-method", "statement": "The alteration in the secretion levels of the remaining 14 proteins (difference between the mean log2 LFQ values >1/1) were evaluated for statistical significance (p < 0.05) utilizing Student's t-test analysis with an FDR value of 0.05 and an S0 correction factor of 0.1, denoted by the black hyperbolic lines (Figure 2C) (24).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32671099", "locator": "sections[7] \"Results\" paragraph 4", "quote": "The alteration in the secretion levels of the remaining 14 proteins (difference between the mean log2 LFQ values >1/1) were evaluated for statistical significance (p < 0.05) utilizing Student's t-test analysis with an FDR value of 0.05 and an S0 correction factor of 0.1, denoted by the black hyperbolic lines (Figure 2C) (24)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Raw MS data has been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD009356.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32671099", "locator": "sections[6] \"Protein ID, Quantification, and Statistical Rationale\" paragraph 2", "quote": "Raw MS data has been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD009356."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:32671099"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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FAH deficiency is associated with Type 1 hereditary tyrosinemia"], ["Proteins unique to SAP"], ["CLEC3B", "Tetranectin", "24.613", "NaN", "NaN", "Binds to Kringle 4 domain of plasminogen. May be involved in the packaging of molecules destined for exocytosis."], ["HSP90AA1", "Heat shock protein HSP 90-alpha", "24.132", "NaN", "NaN", "Molecular chaperone, involved in platelet activation. Extracellularly, mediates immune-regulatory & tissue remodeling."], ["Proteins with increased secretion in STEMI"], ["GPI", "Glucose-6-phosphate isomerase", "24.76", "26.013", "1.171", "Glycolytic enzyme. 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