Trophic Effects of Platelets on Cultured Endothelial Cells are Mediated by Platelet-associated Fibroblast Growth Factor-2 (FGF-2) and Vascular Endothelial Growth Factor (VEGF)

Giuseppe Pintucci; Scott Froum; Jared Pinnell; Paolo Mignatti; Shahin Rafii; David Green

doi:10.1055/s-0037-1613311

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2002; 88(05): 834-842
DOI: 10.1055/s-0037-1613311

Review Article

Schattauer GmbH

Trophic Effects of Platelets on Cultured Endothelial Cells are Mediated by Platelet-associated Fibroblast Growth Factor-2 (FGF-2) and Vascular Endothelial Growth Factor (VEGF)

Giuseppe Pintucci

¹The Seymour Cohn Cardiovascular Surgical Research Laboratory, Division of Cardiothoracic Surgery

,

Scott Froum

²Division of Hematology, Cornell University Medical College, New York, USA

,

Jared Pinnell

²Division of Hematology, Cornell University Medical College, New York, USA

,

Paolo Mignatti

¹The Seymour Cohn Cardiovascular Surgical Research Laboratory, Division of Cardiothoracic Surgery

³Surgery and Cell Biology, New York University Medical Center, New York

,

Shahin Rafii

⁴Division of Hematology and Oncology, Cornell University Medical College, New York, USA

,

David Green

²Division of Hematology, Cornell University Medical College, New York, USA

› Author Affiliations

Abstract

Summary

In addition to their role in primary hemostasis, platelets serve to support and maintain the vascular endothelium. Platelets contain numerous growth factors including the potent angiogenic inducers VEGF and FGF-2. To characterize the function of these two plateletassociated growth factors, the effects of the addition of purified platelets to cultured endothelial cells were examined. The survival and proliferation of endothelial cells were markedly stimulated (2-3-fold and 5-15-fold respectively) by the addition of gel-filtered platelets. Acetylsalicylic acid-treated or lyophilized fixed-platelets were ineffective in supporting endothelial cell proliferation. In Transwell assays, the stimulatory effect of platelets on endothelial cells was preserved, consistent with an effect mediated by secreted factors. The combined inhibition of VEGF and FGF-2 by neutralizing antibodies, in contrast to inhibition of either alone, abrogated both platelet-induced endothelial cell survival and proliferation. FGF-2 isoforms were detected in platelet lysates, as well as in the releasates of agonist-stimulated platelets. Megakaryocytes generated by ex vivo expansion of hematopoietic progenitor cells with kit ligand and thrombopoietin were analyzed for expression of FGF-2. Punctate cytoplasmic staining but no nuclear staining was observed by immunocytochemistry consistent with possible localization of the growth factor to cytoplasmic granules. The addition of platelets to cultured endothelial cells activated extracellular signal-regulated kinase (ERK) in a dose and time-dependent manner. This effect was abrogated by both anti-FGF-2 and anti-VEGF antibody. Since FGF-2 and VEGF are potent angiogenic factors and known endothelial cell survival factors, their release by platelets provides a plausible mechanism for the platelet support of vascular endothelium.

Keywords

Platelets - FGF - VEGF - MAPK

Full Text

References

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