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(Circulation Research. 2005;96:272.)
© 2005 American Heart Association, Inc.

Editorials

HGF and VEGF: A Dynamic Duo

Mary E. Gerritsen

From the Department of Molecular Pharmacology, Exelixis, South San Francisco, Calif.

Correspondence to Mary E. Gerritsen, Department of Molecular Pharmacology, Exelixis, 170 Harbor WAY PO Box 511, South San Francisco, CA 94083. E-mail mgerrits@exelixis.com

See related article, pages 300–307

Key Words: therapeutic angiogenesis • leukocytes • inflammation • antiinflammatory • HGF • VEGF

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The potent, proangiogenic effects of vascular endothelial growth factor (VEGF) have been the focus of many strategies to promote therapeutic angiogenesis. However, the dose-limiting proinflammatory side effects of VEGF (eg, increased vascular permeability, leukocyte adhesion, upregulated adhesion molecule expression) have raised concerns about the clinical utility of VEGF.^1–4 Recently, combinations of VEGF with other growth factors (such as with angiopoeitin-1) have been tested as alternative strategies to promote new vessel growth and limit the edema and inflammation associated with VEGF.⁵

Hepatocyte growth factor (HGF; also known as scatter factor) is a large multidomain protein structurally similar to plasminogen. The receptor for HGF is c-met, a disulphide linked heterodimer with tyrosine kinase activity. HGF is a potent endothelial mitogen, motogen, and morphogen,^6,7 although in contrast to VEGF these effects are not limited to endothelial cells. HGF is induced in skeletal and cardiac muscle after ischemic injury,^8,9 and HGF and its receptor c-met are often overexpressed in various tumors.¹⁰ Administration of HGF, either as a protein or incorporated into an adenoviral vector, has been shown to promote angiogenesis without increased vascular permeability or inflammation.^11–17

Combining HGF and VEGF results in a much more robust endothelial proliferative response and chemotactic response than either growth factor alone.^18,19 In three-dimensional type I collagen gels, neither HGF nor VEGF alone are sufficient to induce human endothelial cell survival and tubulogenesis, yet the combination of the two growth factors will support these responses.¹⁹ In vivo studies also suggest that combining HGF and VEGF also induces a more . . . [Full Text of this Article]

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