Vascular effects of FGF-2 and VEGF-B in rabbits with bilateral hind limb ischemia.
OBJECTIVE
To assess fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor-B (VEGF-B) effects on flow reserve and morphological adaptation in the rabbit ischemic hind limb.


METHODS
Following bilateral femoral artery ligation, calf blood pressure (C(BP)), flow reserve, collateral artery numbers and capillary numbers were assessed. Treatment consisted of rabbit serum albumin (RSA), FGF-2, VEGF-B or FGF-2 + VEGF-B.


RESULTS
Ligation decreased C(BP); on day 14, a 48% deficit remained in the RSA group compared with a deficit of only 22% in FGF-2 and VEGF-B groups. On day 3, flow reserve was attenuated 60%, but recovered by day 14 (with no treatment effects). Collateral artery numbers increased with RSA (+28%), FGF-2 (+53%), VEGF-B (+47%) and FGF-2 + VEGF-B (+59%). Rectus femoris muscle total capillary profiles and fibers per cross-section were alike across groups. Tibialis anterior muscle cross-sectional area was lower with ligation and total capillary number was less in RSA and FGF-2 groups, providing evidence for angiogenesis with VEGF-B. Capillary/muscle fiber ratio was similar in each group.


CONCLUSIONS
FGF-2 and VEGF-B enhanced lower limb perfusion as indicated by improved C(BP) and combined treatment increased collateral artery number. Flow reserve recovery was not enhanced by cytokine treatment. VEGF-B, but not FGF-2, caused angiogenesis in the tibialis anterior muscle. Overall, VEGF-B may have advantages over FGF-2 in this setting; however, their combination may further improve arteriogenesis.
Department of Pharmacology, Cardiovascular Therapeutics Unit, The University of Melbourne, Melbourne, Vic, Australia.
Rafif
R
Wafai
Elizabeth M
EM
Tudor
James A
JA
Angus
Christine E
CE
Wright
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology; D000818:Animals; D005263:Femoral Artery; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology; D008026:Ligation; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011817:Rabbits; D042561:Vascular Endothelial Growth Factor B / Q000627:therapeutic use*
D043925:Angiogenesis Inducing Agents; D042561:Vascular Endothelial Growth Factor B; D016222:Fibroblast Growth Factor 2