Document Detail


pH (low) insertion peptide (pHLIP) targets ischemic myocardium.
MedLine Citation:
PMID:  23248283     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The pH (low) insertion peptide (pHLIP) family enables targeting of cells in tissues with low extracellular pH. Here, we show that ischemic myocardium is targeted, potentially opening a new route to diagnosis and therapy. The experiments were performed using two murine ischemia models: regional ischemia induced by coronary artery occlusion and global low-flow ischemia in isolated hearts. In both models, pH-sensitive pHLIPs [wild type (WT) and Var7] or WT-pHLIP-coated liposomes bind ischemic but not normal regions of myocardium, whereas pH-insensitive, kVar7, and liposomes coated with PEG showed no preference. pHLIP did not influence either the mechanical or the electrical activity of ischemic myocardium. In contrast to other known targeting strategies, the pHLIP-based binding does not require severe myocardial damage. Thus, pHLIP could be used for delivery of pharmaceutical agents or imaging probes to the myocardial regions undergoing brief restrictions of blood supply that do not induce irreversible changes in myocytes.
Authors:
Eugene A Sosunov; Evgeny P Anyukhovsky; Alexander A Sosunov; Anna Moshnikova; Dayanjali Wijesinghe; Donald M Engelman; Yana K Reshetnyak; Oleg A Andreev
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-12-17
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  110     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  2013-02-27     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  82-6     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Columbia University, New York, NY 10032, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Drug Delivery Systems / methods*
Fluorescence
Hydrogen-Ion Concentration
Liposomes / administration & dosage
Male
Membrane Proteins / administration & dosage*
Mice
Mice, Inbred C57BL
Myocardial Ischemia / metabolism*
Myocardium / metabolism*
Grant Support
ID/Acronym/Agency:
CA133890/CA/NCI NIH HHS; GM073857/GM/NIGMS NIH HHS; R01 GM073857/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Liposomes; 0/Membrane Proteins; 0/pHLIP protein
Comments/Corrections

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


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