The main purpose of this project is to investigate the detrimental role of a subgroup of platelets, called Reticulated platelets (RPs), in patients with coronary artery disease (CAD). RPs are young, hyper-reactive platelets with pro-thrombotic potential. High levels of RPs in peripheral blood are predictors of adverse events in different diseases including myocardial infarction. The reason of these correlations is still unclear, and the biology of RPs still has to be investigated. Interestingly, our preliminary analysis of platelet’s RNA in healthy subjects detected a striking upregulation of pro-thrombotic signalling in RPs. We plan to perform a deep characterization of RPs transcriptome with RNA-sequencing in patients with chronic coronary syndrome (CCS) and acute myocardial infarction (MI). In addition, we will validate and correlate these results with proteomic analyses. To further investigate platelet heterogeneity, we aim to characterize the expression of transmembrane receptors with time-of-flight mass cytometry at single-cell level for the first time in CAD patients. These cutting-edge technologies will allow us to investigate platelet heterogeneity with high resolution possibly discovering new subgroups of platelets with different phenotypes. Furthermore, new insights regarding RPs may reveal new therapeutic options leading to more personalized antiplatelet treatment strategies.

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