Dataset Information

Human platelet proteome LC-MS/MS

ABSTRACT: This study aims to elucidate the extent of ex-vivo aspirin-induced acetylation on human platelet proteome from poorly controlled diabetic patients through a shotgun proteomic approach.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Platelet, Platelet

DISEASE(S): Type 2 Diabetes Mellitus

SUBMITTER: Francesco Finamore

LAB HEAD: Jean-Charles Sanchez

PROVIDER: PXD011582 | Pride | 2018-12-19

REPOSITORIES: Pride

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Publications

A high glucose level is associated with decreased aspirin-mediated acetylation of platelet cyclooxygenase (COX)-1 at serine 529: A pilot study.

Finamore Francesco F Reny Jean-Luc JL Malacarne Sarah S Fontana Pierre P Sanchez Jean-Charles JC

Journal of proteomics 20180918

Diabetes is a major risk factor for cardiovascular diseases. Although aspirin is considered a cornerstone of the prevention and treatment of atherothrombotic-related ischemic events, this antiplatelet drug appears to be less effective in patients with poorly controlled diabetes. It has been suggested that the glycation of platelet proteins plays a pivotal role in poor responsiveness to aspirin. However, a direct effect on the critical residue (serine 529, or Ser 529) of the catalytic pocket of c ...[more]

PMID: 30240925

Publication: 1/2

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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. In this case-control study we measured expression levels of platelet miRNAs using microarrays from 40 male patients with premature CAD and 40 age- and sex-matched healthy controls. Premature CAD was defined as a cardiac event before the age of 51 years. The patients were selected from the outpatient clinic of the Academic Medical Center (AMC) of Amsterdam, which is specialised in premature CAD. The control cohort was composed of 40 healthy Caucasian male volunteers, who were recruited by advertisement and who were matched with the cases for age and smoking habits. Individuals of this control cohort did not have a history of CVD, nor did they have a positive family history of CVD and they were not allowed to use any medication. Patients and controls were excluded when they suffered from diabetes. Most CAD patients use aspirin and statins as secondary prevention. The influence of these drugs on miRNA profiles is unknown. To assess the possible influence of medication on miRNA expression and to control for medication as confounding factor, we asked 27 volunteers in our control cohort to also use these drugs. We administered simvastatin 40 mg, once daily, for 6 weeks and during the last two weeks we added 100mg of acetyl salicylic acid, once daily. Blood samples including isolated platelets were collected at baseline in the absence of aspirin and statins and after six weeks of medication use. We also assessed platelet function using the Multiplate® Analyzer (Roche) in the absence of aspirin and statin use. In short, 300 µl whole blood was diluted with 300 µl 0.9% saline and stirred for 3 minutes at 37 ºC. Adenosine diphosphate (ADP) was added in a final concentration of 2.5 ?mol/L to initiate platelet aggregation. Aggregation was measured for 6 minutes and was reported in arbitrary aggregation units plotted against time. Also, the area under the aggregation curve (AUC) was measured. All samples were measured in the absence and presence of 200 ?mol/L indomethacin (20 min incubation with blood) to mimic the effect of aspirin use. We calculated the percentage reduction in AUC after incubation with indomethacin as an in vitro measure of the effect of aspirin use on whole blood platelet aggregation.

Dataset Information

Human platelet proteome LC-MS/MS

Publications

A high glucose level is associated with decreased aspirin-mediated acetylation of platelet cyclooxygenase (COX)-1 at serine 529: A pilot study.

Similar Datasets

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