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Normal ranges of angiogenesis regulatory proteins in human platelets
Author(s) -
Peterson Jon E.,
Zurakowski David,
Italiano Joseph E.,
Michel Lea V.,
Fox Lucius,
Klement Giannoula L.,
Folkman Judah
Publication year - 2010
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.21732
Subject(s) - endostatin , platelet , angiogenesis , thrombospondin , basic fibroblast growth factor , platelet derived growth factor , platelet derived growth factor receptor , growth factor , vascular endothelial growth factor , platelet factor 4 , chemistry , medicine , endocrinology , fibroblast growth factor , immunology , vegf receptors , receptor , metalloproteinase , matrix metalloproteinase
Abstract Platelets sequester angiogenesis regulatory proteins early in tumor growth, which suggests a new avenue for monitoring disease. To date, there are no clinically relevant reference ranges for markers of early angiogenesis. We introduce a new ELISA‐based method for accurate and reproducible measurement of vascular endothelial growth factor (VEGF), platelet‐derived growth factor (PDGF), platelet factor 4 (PF4), thrombospondin‐1 (TSP‐1), fibroblast growth factor, basic (bFGF), and endostatin in platelets. To facilitate clinical applicability, the platelet levels in isolated samples were determined utilizing a new actin ELISA method. Platelets from healthy donors at single and repetitive time points were used for the assessment of normal ranges of these proteins. The physiological levels in platelets were: VEGF (0.74 ± 0.37 pg/10 6 platelets); PDGF (23 ± 6 pg/10 6 ); PF4 (12 ± 5 ng/10 6 ); TSP‐1 (31 ± 12 ng/10 6 ); bFGF (0.44 ± 0.15 pg/10 6 ); and endostatin (5.6 ± 3.0 pg/10 6 ). There was an excellent correlation ( R 2 = 0.7) between the platelet levels calculated with the actin ELISA and complete blood count. The levels of the platelets were higher than those in platelet‐poor plasma by factors of: VEGF (215‐fold); PDGF (914‐fold); PF‐4 (516‐fold); TSP‐1 (813‐fold); and bFGF (17‐fold). The endostatin levels were nearly equivalent. The biovariability of the platelet proteins in eight healthy subjects over a 5‐week period was found to be minimal. We describe accurate and direct measurements of the concentrations of VEGF, bFGF, PDGF, TSP‐1, endostatin, and PF4 in platelets of healthy human subjects. In contrast to the highly variable levels in plasma and serum, the platelet‐derived measurements were accurate and reproducible with minimal biovariability. Am. J. Hematol., 2010. © 2010 Wiley‐Liss, Inc.