title: Basic fibroblast growth factor stimulates angiogenesis in the hindlimb of hyperglycemic rats.
abstract: 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.
authors.affiliation: Surgical Research Laboratory, Department of Surgery, Baystate Medical Center, Tufts University School of Medicine, Springfield, Massachusetts 01199, USA.
authors.forename: J
authors.initials: J
authors.lastname: Stark
authors.forename: R
authors.initials: R
authors.lastname: Baffour
authors.forename: J L
authors.initials: JL
authors.lastname: Garb
authors.forename: J
authors.initials: J
authors.lastname: Kaufman
authors.forename: J
authors.initials: J
authors.lastname: Berman
authors.forename: S
authors.initials: S
authors.lastname: Rhee
authors.forename: M A
authors.initials: MA
authors.lastname: Norris
authors.forename: P
authors.initials: P
authors.lastname: Friedmann
mesh_terms: 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
chemical_list: D016222:Fibroblast Growth Factor 2; D013311:Streptozocin