New Therapeutic Approach For Impaired Arteriogenesis In Diabetic Mouse Hindlimb Ischemia

Background The combined treatment of sustained-release basic fibroblast growth factor (Sr-bFGF) and a 5-hydroxytryptamine-2A blocker, sarpogrelate, was evaluated to see whether it reversed the impaired collateral circulation in diabetic (DM) mouse hindlimb ischemia.Method and Results Diabetic and normal mice with ischemic hindlimb were randomly assigned to I of 5 experimental groups (no treatment, sarpogrelate 50 mg-kg(-1).day(-1), 20,mu g or 50,mu g Sr-bFGF and a combined treatment of 20,mu g Sr-bFGF and sarpogrelate), and treated for 4 weeks. Tissue blood perfusion (TBP), vascular density (angiogenesis) and the number of mature vessels (arteriogenesis) were checked by the use of standard methods. Although angiogenesis was comparable (161 14 vs 1.54 12 vessels/mm(2)), the laser Doppler perfusion image index (LDPII) (0.43 +/- 0.11 (SD) vs 0.63 +/- 0.08, p < 0.05) and arteriogenesis (8 3 vs 12 4 vessels/mm(2), p < 0.05) were significantly lower in DNI mice than those in normal mice. The dose of Sr-bFGF for the sufficient number of mature vessels (>= 45 vessels/mm(2)) and LDPII (>= 0.9) was 20 mu g for the normal mice, and 50 mu g for the DM mice, which was reduced with the aid of sarpogrelate.Conclusions A combined therapy of Sr-bFGF and sarpogrelate is effective for neovascularization to reverse the impaired arteriogenesis and TBP in DM mice.