Document Detail


Adrenomedullin augments collateral development in response to acute ischemia.
MedLine Citation:
PMID:  12788059     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Expression of adrenomedullin, discovered as a vasodilatory peptide, is markedly up-regulated under pathological conditions such as tissue ischemia and inflammation, which are associated with neovascularization. Here, we tested the hypothesis that overly expressed adrenomedullin may augment collateral flow to ischemic tissues. We induced hindlimb ischemia in wild-type mice and injected a naked plasmid expressing human adrenomedullin or an empty vector into the ischemic muscle, followed by in vivo electroporation. Adrenomedullin markedly enhanced blood flow recovery as determined by Laser Doppler imaging. The mice treated with an empty vector suffered frequent autoamputation of the ischemic toe, which was completely prevented by adrenomedullin. Anti-CD31 immunostaining revealed that adrenomedullin significantly increased capillary density. The angiogenic effect of adrenomedullin was abrogated in endothelial nitric oxide synthase (eNOS)-deficient mice. These results indicate that adrenomedullin may promote collateral growth in response to ischemia through activation of eNOS.
Authors:
Minami Abe; Masataka Sata; Hiroaki Nishimatsu; Daisuke Nagata; Etsu Suzuki; Yasuo Terauchi; Takashi Kadowaki; Naoto Minamino; Kenji Kangawa; Hisayuki Matsuo; Yasunobu Hirata; Ryozo Nagai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  306     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-06-05     Completed Date:  2003-07-31     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10-5     Citation Subset:  IM    
Affiliation:
Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Adrenomedullin
Animals
Collateral Circulation / drug effects,  physiology*
Female
Gene Expression
Gene Transfer Techniques
Humans
Ischemia / genetics,  physiopathology*,  therapy*
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Knockout
Neovascularization, Physiologic
Nitric Oxide / physiology
Nitric Oxide Synthase / deficiency,  genetics
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Peptides / genetics,  pharmacology,  physiology*
Recombinant Proteins / genetics
Vasodilation / drug effects
Chemical
Reg. No./Substance:
0/Peptides; 0/Recombinant Proteins; 10102-43-9/Nitric Oxide; 148498-78-6/Adrenomedullin; EC 1.14.13.39/NOS3 protein, human; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, mouse

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