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 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.
Cao
Renhai
R
Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden.
Bråkenhielm
Ebba
E
Pawliuk
Robert
R
Wariaro
David
D
Post
Mark J
MJ
Wahlberg
Eric
E
Leboulch
Philippe
P
Cao
Yihai
Y
D000818:Animals; D000077214:Becaplermin; D001808:Blood Vessels / Q000187:drug effects*; D003097:Collateral Circulation / Q000187:drug effects; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000188:drug therapy*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D011817:Rabbits; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D017479:Receptors, Platelet-Derived Growth Factor