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.


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.
Bir
Shyamal Chandra
SC
Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Fujita
Masatoshi
M
Marui
Akira
A
Hirose
Keiichi
K
Arai
Yoshio
Y
Sakaguchi
Hisashi
H
Huang
Yuhong
Y
Esaki
Jiro
J
Ikeda
Tadashi
T
Tabata
Yasuhiko
Y
Komeda
Masashi
M
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
D017931:DNA Primers; D003692:Delayed-Action Preparations; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D013386:Succinates; D016222:Fibroblast Growth Factor 2; C064294:sarpogrelate