The functional role of blood platelet components in angiogenesis.
The process of neovascularization greatly depends on the induction of the angiogenic phenotype of endothelial cells that is strictly controlled by humoral factors as well as by cellular communications in the vascular system. Although blood platelets contain several secretable pro- and antiangiogenic components, their overall role in angiogenesis remains poorly understood. In a mouse model of hypoxia-induced retinal angiogenesis, the situation of thrombocytopenia as well as inhibition of platelet aggregation by a highly specific alphaIIbbeta3-integrin antagonist or acetyl salicylic acid (Aspirin) administration, respectively, resulted in about 35-50% reduction of retinal neovascularization, compatible with a significant contribution of blood platelets in angiogenesis. Platelet remnants and microvesicles were found at sites of angiogenic sprouts. In vitro isolated platelets incorporated in a fibrin gel induced capillary sprouting of microvascular endothelial cells. Similarly, platelet releasate elevated the permeability of confluent endothelial cell monolayers to the same extent as hypoxia did. Platelet-derived VEGF as well as butanol-extractable lipid mediators were identified as predominant activators of angiogenesis, particularly of microvascular endothelial cell proliferation and migration. In addition, a synergistic effect between platelet-derived VEGF and bFGF in capillary sprouting and endothelial cell proliferation was found. Based on this proangiogenic role of platelets in neovascularization, anti-platelet substances can be considered as potent inhibitors of angiogenesis.
Rhee
Joong-Sup
JS
Biochemisches Institut, Fachbereich Medizin, Justus-Liebig-Universität, Giessen, Germany.
Black
Martin
M
Schubert
Uwe
U
Fischer
Silvia
S
Morgenstern
Eberhard
E
Hammes
Hans-Peter
HP
Preissner
Klaus T
KT
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D016913:Blood Component Transfusion; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology; D004727:Endothelium / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D000860:Hypoxia; D050356:Lipid Metabolism; D051379:Mice; D008854:Microscopy, Electron; D009389:Neovascularization, Pathologic; D010100:Oxygen / Q000737:chemistry; D010641:Phenotype; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D012160:Retina / Q000473:pathology; D015861:Retinal Neovascularization; D013921:Thrombocytopenia; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D042461:Vascular Endothelial Growth Factor A; D001241:Aspirin; D010100:Oxygen