title: 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-hydroxytryptamine(2A) blocker, sarpogrelate, was evaluated to see whether it reversed the impaired collateral circulation in diabetic (DM) mouse hindlimb ischemia.
  
  
  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.
authors: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Shyamal Chandra
authors: SC
authors: Bir
authors: Masatoshi
authors: M
authors: Fujita
authors: Akira
authors: A
authors: Marui
authors: Keiichi
authors: K
authors: Hirose
authors: Yoshio
authors: Y
authors: Arai
authors: Hisashi
authors: H
authors: Sakaguchi
authors: Yuhong
authors: Y
authors: Huang
authors: Jiro
authors: J
authors: Esaki
authors: Tadashi
authors: T
authors: Ikeda
authors: Yasuhiko
authors: Y
authors: Tabata
authors: Masashi
authors: M
authors: Komeda
mesh_terms: D000818:Animals; D001483:Base Sequence; D003097:Collateral Circulation / Q000187:drug effects*; D017931:DNA Primers / Q000235:genetics; D003692:Delayed-Action Preparations; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage; D015870:Gene Expression; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D012702:Serotonin Antagonists / Q000008:administration & dosage; D013386:Succinates / Q000008:administration & dosage
chemical_list: D017931:DNA Primers; D003692:Delayed-Action Preparations; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D013386:Succinates; D016222:Fibroblast Growth Factor 2; C064294:sarpogrelate