Platelets in Healthy and Disease States: From Biomarkers Discovery to Drug Targets Identification by Proteomics

Abstract

Platelets are a heterogeneous small anucleate blood cell population with a central role both in physiological haemostasis and in pathological states, spanning from thrombosis to inflammation, and cancer. Recent advances in proteomic studies provided additional important information concerning the platelet biology and the response of platelets to several pathophysiological pathways. Platelets circulate systemically and can be easily isolated from human samples, making proteomic application very interesting for characterizing the complexity of platelet functions in health and disease as well as for identifying and quantifying potential platelet proteins as biomarkers and novel antiplatelet therapeutic targets. To date, the highly dynamic protein content of platelets has been studied in resting and activated platelets, and several subproteomes have been characterized including platelet-derived microparticles, platelet granules, platelet releasates, platelet membrane proteins, and specific platelet post-translational modifications. In this review, a critical overview is provided on principal platelet proteomic studies focused on platelet biology from signaling to granules content, platelet proteome changes in several diseases, and the impact of drugs on platelet functions. Moreover, recent advances in quantitative platelet proteomics are discussed, emphasizing the importance of targeted quantification methods for more precise, robust and accurate quantification of selected proteins, which might be used as biomarkers for disease diagnosis, prognosis and therapy, and their strong clinical impact in the near future.

Platelet Protein-Related Abnormalities in Response to Acute Hypoglycemia in Type 2 Diabetes

“…Conversely, for P-selectin and heparin cofactor II, it was the T2D males who predominantly drove the differences seen between T2D and controls in the whole group analysis. This is in keeping with other studies where proteomic analysis has shown a multitude of gender-related differences in platelet proteins ( 23 – 25 ), even suggesting mechanistic links to diseases with known gender disparities, such as the increased prevalence of cardiovascular disease in males ( 24 ).…”

Mild hyperlipidemia in mice aggravates platelet responsiveness in thrombus formation and exploration of platelet proteome and lipidome

“…These changes in protein activity can be caused by post-translational modifications (PTMs), which regulate protein activity and are also effective in platelets. These PTMs include phosphorylation, glycosylation, palmitoylation, ubiquitination and oxidative stress, all of which have been described to alter platelet proteins during hemostasis as well as in several diseases including hyperlipidemia 60 . Although both hyperlipidemic mouse strains show a prothrombotic phenotype, we also observed differences between the Apoe −/− and Ldlr −/− platelets in several measurements, as indicated above.…”

Platelet-Adherent Leukocytes Associated With Cutaneous Cross-Reactive Hypersensitivity to Nonsteroidal Anti-Inflammatory Drugs

“…In fact, altered platelet function has been described in severe food-associated respiratory allergy ( Obeso et al, 2018 ), and changes in platelet-related genes have been described in some types of chronic spontaneous urticaria ( Gimenez-Arnau et al, 2017 ). Moreover, platelets have been associated with the etiology of a wide range of pathologies behind coagulation disorders ( Gianazza et al, 2020 ), and some of platelet-related compounds may represent potential biomarkers ( Duarte et al, 2013 ; Eguiluz-Gracia et al, 2018 ; Liao et al, 2018 ; Liao et al, 2020 ; Sokolowska et al, 2020 ).…”