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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:80.)
© 2000 American Heart Association, Inc.

Vascular Biology

Platelet-Activating Factor Enhances Vascular Endothelial Growth Factor–Induced Endothelial Cell Motility and Neoangiogenesis in a Murine Matrigel Model

Giuseppe Montrucchio; Enrico Lupia; Edda Battaglia; Lorenzo Del Sorbo; Mariarosaria Boccellino; Luigi Biancone; Giorgio Emanuelli; Giovanni Camussi

From the Dipartimento di Fisiopatologia Clinica, Università di Torino (G.M., E.L., E.B., L.D.S., G.E.); the Ospedale Gradenigo (E.L.); and the Dipartimento di Medicina Interna, Università di Torino (M.B., L.B., G.C.), Torino, Italy.

Correspondence to Dr G. Camussi, Cattedra di Nefrologia, Dipartimento di Medicina Interna, Corso Dogliotti 14, 10126, Torino, Italy. E-mail giovanni.camussi{at}unito.it

Abstract—We previously reported that platelet-activating factor (PAF) enhances the angiogenic activity of certain polypeptide mediators such as tumor necrosis factor and hepatocyte growth factor by promoting endothelial cell motility. The purpose of the present study was to evaluate whether the synthesis of PAF induced by vascular endothelial growth factor (VEGF) might affect endothelial cell motility, microvascular permeability, and angiogenesis. The neoangiogenesis and synthesis of PAF induced by VEGF were studied in vivo in a murine Matrigel model. Dermal permeability was studied in mice by injection of ¹²⁵I-albumin. The synthesis of PAF, cell motility, and the increased ¹²⁵I-albumin transfer across endothelial monolayers were studied in vitro by using cultures of human umbilical cord vein–derived endothelial cells (HUVECs). The results obtained demonstrate that the neoangiogenesis induced by VEGF in vivo was associated with a local synthesis of PAF and was inhibited by WEB2170 and CV3988, 2 chemically unrelated, specific PAF-receptor antagonists. In contrast, WEB2170 did not inhibit VEGF-enhanced dermal permeability, suggesting that the latter was independent of the synthesis of PAF. In vitro, it was found that VEGF induced the synthesis of PAF by HUVECs in a dose- and time-dependent manner. The cell motility induced by VEGF was inhibited by PAF-receptor antagonists. In contrast, VEGF-induced proliferation of HUVECs and albumin transfer through HUVEC monolayer were unaffected by PAF-receptor antagonists. These results suggest that the synthesis of PAF induced by VEGF enhances endothelial cell migration and contributes to the angiogenic effect of VEGF in the in vivo Matrigel model.

Key Words: vascular endothelial growth factor • platelet-activating factor • angiogenesis

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