Basic fibroblast growth factor stimulates angiogenesis in the hindlimb of hyperglycemic rats.
Angiogenic growth factors including basic fibroblast growth factor (bFGF) have therapeutic value for chronic ischemia in nondiabetic animals. However, angiogenic therapy for chronic ischemia in a background of diabetes remains unexplored. In the present study, we evaluated the effects of exogenous bFGF on angiogenesis in streptozotocin-induced diabetic rats with ischemic and nonischemic limbs. We produced ischemia of the left lower limb by excising the superficial femoral artery. At 2 weeks, the rats received an intramuscular injection of vehicle (group A), 0.3 microg bFGF/day (group B), or 1 microg bFGF/day (group C), daily for 2 weeks. At 4 weeks, we assessed limb angiogenesis by skeletal muscle capillary density (cap/mm2) and capillary per muscle fiber ratio (cap/F) counts. Group C had significantly higher mean levels compared to group A for calf capillary density (P < 0.0024) and capillary per muscle fiber ratio in both thigh (P < 0.0015) and calf (P < 0.0001). There was a trend toward increased mean capillary per muscle fiber ratio with increasing dose. This trend was significant in the calf (P < 0.0015) and just missed statistical significance in the thigh. There was a similar trend in calf capillary density. We conclude that exogenous bFGF enhances angiogenesis and, possibly, collateral circulation in ischemic limbs of diabetic rats.
Stark
J
J
Surgical Research Laboratory, Department of Surgery, Baystate Medical Center, Tufts University School of Medicine, Springfield, Massachusetts 01199, USA.
Baffour
R
R
Garb
J L
JL
Kaufman
J
J
Berman
J
J
Rhee
S
S
Norris
M A
MA
Friedmann
P
P
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D016222:Fibroblast Growth Factor 2; D013311:Streptozocin