title: Early sustained injections of erythropoietin improve angiogenesis and restoration of perfusion in the ischemic mouse hindlimb.
abstract: This study was conducted to investigate the effects of erythropoietin (Epo) on both acute and chronic limb ischemia (ALI and CLI) and to evaluate the differences in mechanisms according to the method of Epo administration. Hindlimb ischemia was made in BALB/c mice with femoral artery ligation. The mice were divided into four groups: Group 1 (control, no treatment), Group 2 (ALI, early multiple doses), Group 3 (ALI, early single high dose), Group 4 (CLI, late multiple doses). Blood flow ratio significantly increased in Group 2 in 4 weeks. Expression of pAkt and Erythropoietin receptor were significantly higher in Group 2 on postoperative day (POD) 7. The number of CD31- and vascular endothelial growth factor-positive cells were significantly higher in Group 2 on POD 7 and 56. Group 3 and 4 showed a tendency of higher cell counts than the control. The early sustained Epo was effective in improving blood flow through angiogenesis. In chronic phase, weekly multiple dosing of Epo induced angiogenesis, however, the blood flow ratio did not increase significantly. The results of this study suggest that Epo administration during the acute phase followed by maintenance for several days may be important for increasing blood flow and angiogenesis.
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Ahn
authors.forename: Seung-Kee
authors.initials: SK
authors.lastname: Min
authors.forename: Sang-Il
authors.initials: SI
authors.lastname: Min
authors.forename: Ja Hee
authors.initials: JH
authors.lastname: Suh
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jongwon
authors.initials: J
authors.lastname: Ha
mesh_terms: D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D004921:Erythropoietin / Q000494:pharmacology*; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C103998:epoetin beta; D004921:Erythropoietin; D051057:Proto-Oncogene Proteins c-akt