Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions.
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.
Coppinger
Judith A
JA
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, 123 St Stephen's Green, Dublin 2, Ireland.
Cagney
Gerard
G
Toomey
Sinead
S
Kislinger
Thomas
T
Belton
Orina
O
McRedmond
James P
JP
Cahill
Dolores J
DJ
Emili
Andrew
A
Fitzgerald
Desmond J
DJ
Maguire
Patricia B
PB
D001161:Arteriosclerosis / Q000378:metabolism* / Q000503:physiopathology*; D001792:Blood Platelets / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002864:Chromogranins; D021984:Cyclophilin A / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D015539:Platelet Activation / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D040901:Proteomics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D002135:Calcium-Binding Proteins; C107182:Calu protein, mouse; D002864:Chromogranins; D011506:Proteins; D021984:Cyclophilin A