The functional role of blood platelet components in angiogenesis

Joong-Sup Rhee; Martin Black; Uwe Silvia; Silvia Fischer; Eberhard Morgenstern; Hans-Peter Hammes; Klaus T. Preissner

doi:10.1160/TH03-04-0213

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(02): 394-402
DOI: 10.1160/TH03-04-0213

Endothelium and Vascular Development

Schattauer GmbH

The functional role of blood platelet components in angiogenesis

Joong-Sup Rhee^*

,

Martin Black^*

,

Uwe Silvia

,

Silvia Fischer

¹Biochemisches Institut, Fachbereich Medizin, Justus-Liebig-Universität, Giessen; Max-Planck-Institut, Experimentelle Kardiologie, Bad Nauheim

,

Eberhard Morgenstern

²Medizinische Biologie, Universität des Saarlandes, Homburg/Saar

,

Hans-Peter Hammes

³Medizinische Klinik V, Universitätsklinikum, Mannheim, Germany

,

Klaus T. Preissner

› Author Affiliations

Abstract

Summary

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 αIIbß3-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-derivedVEGF 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.

Keywords

Vascular endothelial growth factor - retinal neovascularization - lysophospholipids - thrombocytopenia - anti-platelet drugs

Full Text

References

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