New therapeutic approach for impaired arteriogenesis in diabetic mouse hindlimb ischemia

Abstract

Background: The combined treatment of sustained-release basic fibroblast growth factor (Sr-bFGF) and a 5-hydroxytryptamine2A 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 1 of 5 experimental groups (no treatment, sarpogrelate 50mg·kg -1·day-1, 20μg or 50μg Sr-bFGF and a combined treatment of 20μg 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 154±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/mm2, p<0.05) were significantly lower in DM mice than those in normal mice. The dose of Sr-bFGF for the sufficient number of mature vessels (≥45 vessels/mm2) and LDPII (≥0.9) was 20μg for the normal mice, and 50μg for the DM mice, which was reduced widi 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.