Document Detail


Tissue kallikrein and kinin infusion promotes neovascularization in limb ischemia.
MedLine Citation:
PMID:  18627294     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adenovirus-mediated kallikrein delivery has been shown to promote blood vessel growth in the limb under both ischemic and normoperfused conditions. Here we investigated whether a continuous supply of kallikrein and kinin peptide can induce neovascularization in a rat model of hindlimb ischemia. Rats underwent femoral artery ligation and localized injection of tissue kallikrein, bradykinin or B1 receptor agonist, followed by infusion of proteins by osmotic minipump. Regional blood flow was monitored weekly by laser Doppler perfusion imaging. Three weeks after surgery, rats receiving kallikrein and kinins showed a significant increase in the perfusion ratio of ischemic vs. normoperfused limb compared to control rats. Similarly, a microsphere assay showed that kallikrein and kinins significantly increased regional blood flow without altering blood pressure. Moreover, kallikrein and kinins significantly augmented capillary and arteriole densities, as quantified by immunostaining with CD-31 and smooth muscle alpha-actin. Both tissue kallikrein and bradykinin increased hemoglobin content in Matrigel implants in mice, providing further evidence of the angiogenic properties. Kinins, when delivered subcutaneously via Matrigel in rats, also increased regional perfusion. This is the first demonstration that local application of tissue kallikrein protein or kinin peptide has therapeutic value in the treatment of ischemic disease by promoting neovascularization.
Authors:
Robert S Smith; Lin Gao; Lee Chao; Julie Chao
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Biological chemistry     Volume:  389     ISSN:  1431-6730     ISO Abbreviation:  Biol. Chem.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-09-04     Completed Date:  2008-09-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9700112     Medline TA:  Biol Chem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  725-30     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arterioles / growth & development
Capillaries / growth & development
Collagen
Drug Combinations
Hemoglobins / metabolism
Hindlimb / blood supply*,  drug effects,  physiopathology*
Injections
Ischemia / physiopathology*
Kinins / administration & dosage,  pharmacology*
Laminin
Lasers
Male
Microspheres
Neovascularization, Physiologic / drug effects*
Peptides / administration & dosage,  pharmacology
Perfusion
Proteoglycans
Rats
Receptor, Bradykinin B1 / antagonists & inhibitors
Receptor, Bradykinin B2 / antagonists & inhibitors
Tissue Kallikreins / administration & dosage,  pharmacology*
Grant Support
ID/Acronym/Agency:
C06 RR015455/RR/NCRR NIH HHS; DK-066250/DK/NIDDK NIH HHS; HL-29373/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Drug Combinations; 0/Hemoglobins; 0/Kinins; 0/Laminin; 0/Peptides; 0/Proteoglycans; 0/Receptor, Bradykinin B1; 0/Receptor, Bradykinin B2; 119978-18-6/matrigel; 9007-34-5/Collagen; EC 3.4.21.35/Tissue Kallikreins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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