In vitro release of vascular endothelial growth factor during platelet aggregation.
Platelet aggregation is a cardinal feature of both vascular repair and vascular disease. During aggregation platelets release a variety of vasoactive substances; some of these promote angiogenesis, endothelial permeability, and endothelial growth, actions shared by vascular endothelial growth factor (VEGF). This study was undertaken to investigate the hypothesis that VEGF is released by aggregating platelets. We found that VEGF was secreted during the in vitro aggregation of platelet-rich plasma induced by thrombin, collagen, epinephrine, and ADP (range 23-518 pg VEGF/ml). Furthermore, serum VEGF levels were elevated compared with plasma (230 +/- 63 vs. 38 +/- 8 pg VEGF/ml), indicative of VEGF release during whole blood coagulation. Lysates of apheresed, leukocyte-poor platelet units contained significant amounts of VEGF (2.4 +/- 0.8 pg VEGF/mg protein). VEGF message and protein were also present in a megakaryocytic cell line (Dami cell). These results suggest constitutive roles for platelet VEGF in the repair of intimal vessel injury and in the altered permeability and intimal proliferation seen at sites of platelet aggregation and thrombosis.
Department of Pulmonary Sciences, University of Colorado School of Medicine and the Bonfils Blood Center, Denver, Colorado 80262, USA.
J P
JP
Maloney
C C
CC
Silliman
D R
DR
Ambruso
J
J
Wang
R M
RM
Tuder
N F
NF
Voelkel
D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D003094:Collagen / Q000494:pharmacology; D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008222:Lymphokines / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008533:Megakaryocytes / Q000378:metabolism; D010949:Plasma / Q000737:chemistry; D010974:Platelet Aggregation / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D013917:Thrombin / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000244:Adenosine Diphosphate; D003094:Collagen; D013917:Thrombin; D004837:Epinephrine