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Blood, 15 March 2002, Vol. 99, No. 6, pp. 2045-2053
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Platelet-derived growth factor inhibits basic fibroblast growth
factor angiogenic properties in vitro and in vivo through its  receptor
Francesco De Marchis,
Domenico Ribatti,
Claudia Giampietri,
Alessandro Lentini,
Debora Faraone,
Marco Scoccianti,
Maurizio C. Capogrossi, and
Antonio Facchiano
From the Laboratorio di Patologia Vascolare, Istituto
Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere
Scientifico, Rome; Dipartimento Anatomia Umana e Istologia,
Università degli Studi, Bari; Dipartimento Istologia ed
Embriologia Medica, Università La Sapienza, Rome; Dipartimento
Biologia, Università Tor Vergata, Rome; and Dipartimento
Chirurgia Vascolare, Ospedale San Giovanni-Addolorata, Rome, Italy.
Basic fibroblast growth factor (bFGF) and platelet-derived growth
factor-BB (PDGF-BB) modulate vascular wall cell function in vitro and
angiogenesis in vivo. The aim of the current study was to determine how
bovine aorta endothelial cells (BAECs) respond to the simultaneous
exposure to PDGF-BB and bFGF. It was found that bFGF-dependent BAEC
migration, proliferation, and differentiation into tubelike structures
on reconstituted extracellular matrix (Matrigel) were inhibited by
PDGF-BB. The role played by PDGF receptor  (PDGF-R) was
investigated by selective stimulation with PDGF-AA, by blocking
PDGF-BB-binding to PDGF-R with neomycin, or by transfecting
cells with dominant-negative forms of the receptors to
selectively impair either PDGF-R or PDGF-R function. In all cases, PDGF-R impairment abolished the inhibitory effect of PDGF-BB on bFGF-directed BAEC migration. In addition, PDGF-R phosphorylation was increased in the presence of bFGF and PDGF, as compared to PDGF
alone, whereas mitogen-activated protein kinase phosphorylation was
decreased in the presence of PDGF-BB and bFGF compared with bFGF alone.
In vivo experiments showed that PDGF-BB and PDGF-AA inhibited
bFGF-induced angiogenesis in vivo in the chick embryo chorioallantoic
membrane assay and that PDGF-BB inhibited bFGF-induced angiogenesis in
Matrigel plugs injected subcutaneously in CD1 mice. Taken together
these results show that PDGF inhibits the angiogenic properties of bFGF
in vitro and in vivo, likely through PDGF-R stimulation.
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