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Article
Nature Medicine  9, 604 - 613 (2003)
Published online: 31 March 2003; | doi:10.1038/nm848

Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2

Renhai Cao1, Ebba Bråkenhielm1, Robert Pawliuk2, David Wariaro3, Mark J. Post4, Eric Wahlberg3, Philippe Leboulch2, 5, 6 & Yihai Cao1

1  Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden

2  Genetix Pharmaceuticals, Inc., Cambridge, Massachusetts, USA

3  Department of Vascular Surgery, Karolinska Hospital, Stockholm, Sweden

4  Department of Medicine, Dartmouth Medical School, Lebanon, New Hampshire, USA

5  Harvard Medical School and Division of Genetics, Department of Medicine, Brigham & Women's Hospital, Boston, Massachusetts, USA

6  INSERM EMI 0111, Hopital Saint-Louis, Paris, France

Correspondence should be addressed to Yihai Cao yihai.cao@mtc.ki.se
The establishment of functional and stable vascular networks is essential for angiogenic therapy. Here we report that a combination of two angiogenic factors, platelet-derived growth factor (PDGF)-BB and fibroblast growth factor (FGF)-2, synergistically induces vascular networks, which remain stable for more than a year even after depletion of angiogenic factors. In both rat and rabbit ischemic hind limb models, PDGF-BB and FGF-2 together markedly stimulated collateral arteriogenesis after ligation of the femoral artery, with a significant increase in vascularization and improvement in paw blood flow. A possible mechanism of angiogenic synergism between PDGF-BB and FGF-2 involves upregulation of the expression of PDGF receptor (PDGFR)-alpha and PDGFR-beta by FGF-2 in newly formed blood vessels. Our data show that a specific combination of angiogenic factors establishes functional and stable vascular networks, and provides guidance for the ongoing clinical trials of angiogenic factors for the treatment of ischemic diseases.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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