Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of P
Author: ["Renhai Cao","Ebba Bråkenhielm","Robert Pawliuk","David Wariaro","Mark J. Post","Eric Wahlberg","Philippe Leboulch","Yihai Cao"]
Publication: Nature Medicine
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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)-α and PDGFR-β 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.
Cite this article
Cao, R., Bråkenhielm, E., Pawliuk, R. et al. Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2. Nat Med 9, 604–613 (2003). https://doi.org/10.1038/nm848
