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

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          Abstract

          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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          Author and article information

          Journal
          Nat Med
          Nature medicine
          Springer Science and Business Media LLC
          1078-8956
          1078-8956
          May 2003
          : 9
          : 5
          Affiliations
          [1 ] Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
          Article
          nm848
          10.1038/nm848
          12669032
          c6593b5a-e83c-4762-84f0-e269146f80b5
          History

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