Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions

Abstract

Proteins secreted by activated platelets can adhere to the vessel wall and promote the development of atherosclerosis and thrombosis. Despite this biologic significance, however, the complement of proteins comprising the platelet releasate is largely unknown. Using a proteomics approach, we have identified more than 300 proteins released by human platelets following thrombin activation. Many of the proteins identified were not previously attributed to platelets, including secretogranin III, a potential monocyte chemoattractant precursor; cyclophilin A, a vascular smooth muscle cell growth factor; calumenin, an inhibitor of the vitamin K epoxide reductase-warfarin interaction, as well as proteins of unknown function that map to expressed sequence tags. Secretogranin III, cyclophilin A, and calumenin were confirmed to localize in platelets and to be released upon activation. Furthermore, while absent in normal vasculature, they were identified in human atherosclerotic lesions. Therefore, these and other proteins released from platelets may contribute to atherosclerosis and to the thrombosis that complicates the disease. Moreover, as soluble extracellular proteins, they may prove suitable as novel therapeutic targets.

Recent advances in blood‐related proteomics

“…The global characterization of these released proteins is called "secretome" [128,129]. The study of the secretome is important, because it contains peptides with paracrine or autocrine functions and peptides with prothrombotic properties.…”

Thrombin-dependent intravascular leukocyte trafficking regulated by fibrin and the platelet receptors GPIb and PAR4

“…PARs are found on the surface of many cell types including platelets, endothelial cells, smooth muscle cells as well as effector cells of the immune system 4,5 . Thrombin activation of platelets through PARs is central to their haemostatic and prothrombotic functions 6,7 and leads to the generation and release of a broad range of proinflammatory molecules 8,9 . Thrombin activation of endothelial and immune effector cells induces the production of several growth factors, chemokines and cytokines 4,10,11 and also alters their adhesive phenotype 12,13 .…”

The TRPV1 ion channel is expressed in human but not mouse platelets

“…Our Western blot studies have been independently reproduced by Savini et al using a different antibody [2]. Furthermore, TRPV1 has also been identified in a human platelet proteomic study [3,4] . These earlier studies are, however, yet to address the role that this non-selective cation channel might play in regulating platelet activity in vivo.…”

“…The TRPV1 ion channel is expressed in human but not mouse platelets Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK, 2 Department of Physiology, University of Extremadura, Caceres, Spain, and 3 Institute for Science and Technology in Medicine, Keele University, Hartshill, UK…”