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Asialoerythropoietin Exerts Stronger Angiogenic Activity than Erythropoietin Via its Binding Affinity to Tissue.
MedLine Citation:
PMID:  23314760     Owner:  NLM     Status:  Publisher    
PURPOSE: Although erythropoietin (EPO) is known to express angiogenic and cardioprotective effects, it also induces hypertension, polycythemia, and platelet activation, which may cause serious adverse effects in patients with cardiovascular diseases. We compared the angiogenic effects of EPO and its nonerythropoietic derivative, asialo-EPO (AEPO). METHODS: Lower limb ischemia was induced in ICR and C57/BL mice. Mice were injected intramuscularly with 2 μg/kg of EPO derivatives for 6 or 7 days. To assess biological differences, the tissue affinity of both EPO derivatives was analyzed in vitro using heparin affinity column chromatography. Tissue affinity was also analyzed in vivo using an intramuscular pharmacokinetic study. RESULTS: The survival of ischemic legs was better in the AEPO group than that in the EPO group (5/13 = 38.5 % vs 1/13 = 7.7 %, p < 0.05), and an increase in regenerated vessels was observed in the AEPO group, but not in the EPO group in ICR mice. Vessel/muscle ratios in control, EPO, and AEPO groups were 0.50 ± 0.34, 0.61 ± 0.32, and 2.83 ± 1.13, respectively (p < 0.0001). On the other hand, regenerated vessels were observed in both EPO and AEPO groups (p < 0.001) in C57/BL mice. AEPO, but not EPO, expressed heparin affinity in vitro. Intramuscularly injected EPO gradually decreased in muscle tissue, while AEPO was maintained at 2.5 ng/muscle for 1 day after several hours of a rapid clearance phase in vivo. CONCLUSIONS: AEPO exerts stronger angiogenic effects than those of EPO presumably via its tissue affinity. Administration of AEPO is a promising option for the treatment of patients with critical limb ischemia.
Takao Yanagawa; Ken Toba; Kiminori Kato; Tomoyasu Suzuki; Shiro Minagawa; Takashi Saigawa; Takuya Ozawa; Masato Oda; Tsugumi Takayama; Haruo Hanawa; Masato Higuchi; Hideki Saito; Yoshifusa Aizawa
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-13
Journal Detail:
Title:  Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy     Volume:  -     ISSN:  1573-7241     ISO Abbreviation:  Cardiovasc Drugs Ther     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712220     Medline TA:  Cardiovasc Drugs Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
First Department of Internal Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan.
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