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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-07-2315.
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Blood, 15 April 2003, Vol. 101, No. 8, pp. 3014-3020
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
The tetrapeptide AcSDKP, an inhibitor of primitive hematopoietic
cell proliferation, induces angiogenesis in vitro and in
vivo
Jian-Miao Liu,
Françoise Lawrence,
Milica Kovacevic,
Jérôme Bignon,
Evangelia Papadimitriou,
Jean-Yves Lallemand,
Panagiotis Katsoris,
Pierre Potier,
Yves Fromes, and
Joanna Wdzieczak-Bakala
From the Institut de Chimie des Substances Naturelles,
Centre National de la Recherche Scientifique (CNRS), Gif-sur-Yvette,
France; Laboratory of Molecular Pharmacology, Department
of Pharmacy, University of Patras, Patras, Greece;
Division of Genetics, Cell and Developmental Biology, Department of
Biology, University of Patras, Patras, Greece; and
Institut de Myologie, INSERM U523, Paris, France.
The tetrapeptide acetyl-Ser-Asp-Lys-Pro (AcSDKP), purified from
bone marrow and constitutively synthesized in vivo, belongs to the
family of negative regulators of hematopoiesis. It protects the stem
cell compartment from the toxicity of anticancer drugs and irradiation
and consequently contributes to a reduction in marrow failure. This
current work provides experimental evidence for another novel biologic
function of AcSDKP. We report that AcSDKP is a mediator of
angiogenesis, as measured by its ability to modulate endothelial cell
function in vitro and angiogenesis in vivo. AcSDKP at nanomolar
concentrations stimulates in vitro endothelial cell migration and
differentiation into capillary-like structures on Matrigel as well as
enhances the secretion of an active form of matrix metalloproteinase-1
(MMP-1). In vivo, AcSDKP promotes a significant angiogenic response in
the chicken embryo chorioallantoic membrane (CAM) and in the abdominal
muscle of the rat. Moreover, it induces the formation of blood vessels
in Matrigel plugs implanted subcutaneously in the rat. This is the first report demonstrating the ability of AcSDKP to interact directly with endothelial cells and to elicit an angiogenic response in vitro
and in vivo.
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