Differential Expression Of Platelet Proteins In Stable Unstable Coronary Artery Disease and Acute Coronary Syndromes

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Abstract Background In coronary artery disease (CAD), the risk of platelet-mediated coronary thrombosis varies over time, with the risk of events falling in the months following an episode of acute coronary syndrome (ACS). This study aims to characterize the platelet protein signature that differentiates stable CAD and ACS so as to identify when a patient with stable CAD is at risk for ACS. Methods We studied 2 groups of patients (N=10) undergoing PCI for CAD; patients with ACS (NSTEMI, STEMI), and patients with stable CAD undergoing PCI. All patients received a standard antiplatelet regimen of clopidogrel or prasugrel and aspirin. Samples were obtained immediately following PCI (days 1-3) and at follow-up (30-60 days). Total platelet lysate and secreted proteins following TRAP-induced platelet activation were extracted and the proteins trypsin-digested prior to analysis by liquid chromatography coupled to high resolution, high mass accuracy Orbitrap mass spectrometry. Protein identities and relative quantitation were determined in a label-free approach, using the MaxQuant suite of programs. Results Lysates: In total 1585 proteins were identified in platelet lysates. Comparing the 2 groups at PCI, there were 266 proteins differentially expressed between stable CAD and ACS; these are enriched in several ontology categories including coagulation and platelet activation. At follow up, 167 proteins were differentially expressed between groups -up, including a cluster of proteins involved in signal transduction. Secreted proteins In total 258 proteins were detected in TRAP-induced platelet secretion samples. Clustering analysis of samples from ACS (both PCI and follow up) showed that these patients largely clustered together in that they exhibited a consistent pattern of protein expression. Interestingly, a subgroup of samples from patients with stable CAD was closely related to ACS samples (Figure). Discussion Clustering of secreted platelet protein profiles indicates a common pattern of expression in patients with ACS. A subset of stable CAD patients has a similar pattern, and these patients may be at increased risk of thrombosis. Replication of this signature of protein expression in other patient populations and prospective analysis of risk will be required to address its applicability in the assessment of patients with CAD. Disclosures: No relevant conflicts of interest to declare.

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