Label Free Proteomics Profiling Unveils Downregulation of Thrombin Mediated Signaling and Aggregation of Human Platelets upon Treatment with Thrombin Inhibitors

摘要

Global changes in protein expression profiles in human platelets treated with novel peptidic DTI drugs in the presence of thrombin were analyzed using the label free quantification (LFQ) method, using nanoLC-MS/MS on a Q-Exactive-Orbitrap mass spectrometer. The IPA analysis confirmed that several proteins involved in the actin, ILK, rhoA, rhoGDI and integrin signaling pathways were statistically significant (p<0.001-0.05), i.e., at least three fold down-regulated in the DTI-treated platelets. These data show that the newly-designed DTI are effective inhibitors of thrombin-activated platelet aggregation, and further advocate for an expanded use of label-free (LFQ) global proteomics profiling as a highly reliable assay capable of monitoring the efficiency of selected drug treatment(s) during ACS management.