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

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...

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Veröffentlicht in:Nature medicine 2003-05, Vol.9 (5), p.604-613
Hauptverfasser: Cao, Renhai, Bråkenhielm, Ebba, Pawliuk, Robert, Wariaro, David, Post, Mark J., Wahlberg, Eric, Leboulch, Philippe, Cao, Yihai
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container_end_page 613
container_issue 5
container_start_page 604
container_title Nature medicine
container_volume 9
creator Cao, Renhai
Bråkenhielm, Ebba
Pawliuk, Robert
Wariaro, David
Post, Mark J.
Wahlberg, Eric
Leboulch, Philippe
Cao, Yihai
description 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.
doi_str_mv 10.1038/nm848
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source MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online
subjects Animals
Biomedical and Life Sciences
Biomedicine
Blood Vessels - drug effects
Cancer Research
Collateral Circulation - drug effects
Drug Synergism
Fibroblast Growth Factor 2 - pharmacology
Hindlimb - blood supply
Infectious Diseases
Ischemia - drug therapy
Metabolic Diseases
Mice
Molecular Medicine
Neovascularization, Physiologic - drug effects
Neurosciences
Platelet-Derived Growth Factor - pharmacology
Proto-Oncogene Proteins c-sis
Rabbits
Rats
Receptors, Platelet-Derived Growth Factor - biosynthesis
Synergism
title Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2
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