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-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 no...

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Bibliographic Details
Published in:Circulation Journal 2007, Vol.72(4), pp.633-640
Main Authors: Bir, Shyamal Chandra, Fujita, Masatoshi, Marui, Akira, Hirose, Keiichi, Arai, Yoshio, Sakaguchi, Hisashi, Huang, Yuhong, Esaki, Jiro, Ikeda, Tadashi, Tabata, Yasuhiko, Komeda, Masashi
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Collateral Circulation - drug effects
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
Diabetic mouse
DNA Primers - genetics
Fibroblast Growth Factor 2 - administration & dosage
Gene Expression
Growth factors
Hindlimb - blood supply
Hindlimb ischemia
Ischemia - complications
Ischemia - drug therapy
Ischemia - genetics
Ischemia - pathology
Male
Mice
Mice, Inbred C57BL
Neovascularization
Neovascularization, Physiologic - drug effects
Receptor, Serotonin, 5-HT2A - genetics
Serotonin Antagonists - administration & dosage
Serotonin blocker
Succinates - administration & dosage
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Summary: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 50 mg · kg-1 · day-1, 20 μg or 50 μg Sr-bFGF and a combined treatment of 20 μg 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/mm2), the laser Doppler perfusion image index (LDPII) (0.43±0.11 (SD) vs 0.63±0.08, p
ISSN:1346-9843
1347-4820
DOI:10.1253/circj.72.633