They also estimated the copy number of 3718 proteins in their sample, using a normalized spectral abundance factor; this reflects the spectral count of a protein versus its length as a measure of its abundance. This estimation ranged from 2.2 × 106 to less than 500 proteins. In addition, they also assessed the proteome variation C59 wnt by relative quantitative mass spectrometry in platelets isolated from 4 different donors. They concluded that 85% of the 1900 proteins quantified showed almost no biological variation. This type of work represents a baseline for any project dedicated to the study of platelet function. Of note, data mining is an essential

step after proteomic analysis and the integration of the protein–protein interactions to construct the identified pathways is called systems strategy AZD5363 order and allows identifying clusters, i.e. groups of proteins, for further functional validation [62]. Proteomics has been used to study several

diseases triggered by genetic variants and affecting platelet reactivity, such as gray platelet syndrome [63] or cystic fibrosis [64]. Other pathologies associated with platelet function modulation were also explored, such as arterial thrombosis [65] or acute coronary syndrome [66]. Proteomics was also used to investigate the impact of aspirin or clopidogrel on platelet function [67] [68]. However, there is limited proteomics data

regarding the investigation of platelet reactivity variability. Mannose-binding protein-associated serine protease The proteins involved in the cytoskeleton (gelsolin precursor isotype 2 and 3, and F-actin capping protein isotype 1) were found by 2-dimensional gel electrophoresis down-regulated in stable cardiovascular patients under aspirin treatment and presenting a high platelet reactivity. This had been assessed using a Platelet Function Analyzer 100 (PFA-100™, Siemens, Marburg, Germany) [69]. These patients also showed a modulation of proteins involved in glycolysis (GAPDH and 1,6-bisphosphate aldolase) and in oxidative stress (heat shock protein 71 and 60, and glutathione S-transferase), which could lead to an increased turnover of platelets and might explain a poor response to aspirin treatment. As described above, several studies tried to identify genes potentially responsible for the variability of platelet reactivity in CV patients or in healthy subjects. They used several methods to select patients and several analytical approaches based on SNPs [32], [48], [49], [70] and [71], proteins [69], or a combination of the two [57]. However, they all focused on gene products taken separately. In addition, apart from a few exceptions such as PEAR1 or GP6, patient samples from these different studies may show inconsistency at the gene product level, but more homogeneity at the level of the pathways they belong to.