New therapeutic approach for impaired arteriogenesis in diabetic mouse hindlimb ischemia

Circ J. 2008 Apr;72(4):633-40. doi: 10.1253/circj.72.633.


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 1 of 5 experimental groups (no treatment, sarpogrelate 50 mg . kg(-1) . day(-1), 20 microg or 50 microg Sr-bFGF and a combined treatment of 20 microg 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/mm(2), 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 (>or=45 vessels/mm(2)) and LDPII (>or=0.9) was 20 microg for the normal mice, and 50 microg 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Collateral Circulation / drug effects*
  • DNA Primers / genetics
  • Delayed-Action Preparations
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Angiopathies / drug therapy
  • Diabetic Angiopathies / genetics
  • Diabetic Angiopathies / pathology
  • Fibroblast Growth Factor 2 / administration & dosage
  • Gene Expression
  • Hindlimb / blood supply
  • Ischemia / complications
  • Ischemia / drug therapy*
  • Ischemia / genetics
  • Ischemia / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic / drug effects*
  • Receptor, Serotonin, 5-HT2A / genetics
  • Serotonin Antagonists / administration & dosage
  • Succinates / administration & dosage


  • DNA Primers
  • Delayed-Action Preparations
  • Receptor, Serotonin, 5-HT2A
  • Serotonin Antagonists
  • Succinates
  • Fibroblast Growth Factor 2
  • sarpogrelate