| Dipyridamole reverses peripheral ischemia and induces angiogenesis in the Db/Db diabetic mouse hind-limb model by decreasing oxidative stress. | |
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MedLine Citation:
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PMID: 21070849 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Dipyridamole anti-platelet therapy has previously been suggested to ameliorate chronic tissue ischemia in healthy animals. However, it is not known if dipyridamole therapy represents a viable approach to alleviating chronic peripheral tissue ischemia associated with type 2 diabetes. Here we examine the hypothesis that dipyridamole treatment restores reperfusion of chronic hind-limb ischemia in the murine B6.BKS-Lepr(db/db) diabetic model. Dipyridamole therapy quickly rectified ischemic hind-limb blood flow to near preligation levels within 3 days of the start of therapy. Restoration of ischemic tissue blood flow was associated with increased vascular density and endothelial cell proliferation observed only in ischemic limbs. Dipyridamole significantly increased total nitric oxide metabolite levels in tissue, which were not associated with changes in endothelial NO synthase expression or phosphorylation. Interestingly, dipyridamole therapy significantly decreased ischemic tissue superoxide and protein carbonyl levels, identifying a dominant antioxidant mechanistic response. Dipyridamole therapy also moderately reduced diabetic hyperglycemia and attenuated development of dyslipidemia over time. Together, these data reveal that dipyridamole therapy is an effective modality for the treatment of chronic tissue ischemia during diabetes and highlights the importance of dipyridamole antioxidant activity in restoring tissue NO bioavailability during diabetes. |
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Authors:
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Christopher B Pattillo; Shyamal C Bir; Billy G Branch; Eric Greber; Xinggui Shen; Sibile Pardue; Rakesh P Patel; Christopher G Kevil |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-11-09 |
Journal Detail:
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Title: Free radical biology & medicine Volume: 50 ISSN: 1873-4596 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: United States |
Other Details:
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Languages: eng Pagination: 262-9 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Pathology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA 71130, USA. |
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Descriptor/Qualifier:
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| Grant Support | |
ID/Acronym/Agency:
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HL080482/HL/NHLBI NIH HHS; HL094021/HL/NHLBI NIH HHS |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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