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pH (low) insertion peptide (pHLIP) targets ischemic myocardium

Evgeny A. Sosunov; Evgeny P. Anyukhovsky; Alexander A. Sosunov; Anna Moshnikova; Dayanjali Wijesinghe; Donald M. Engelman; Yana K. Reshetnyak; Oleg A. Andreev

Title:
pH (low) insertion peptide (pHLIP) targets ischemic myocardium
Author(s):
Sosunov, Evgeny A.
Anyukhovsky, Evgeny P.
Sosunov, Alexander A.
Moshnikova, Anna
Wijesinghe, Dayanjali
Engelman, Donald M.
Reshetnyak, Yana K.
Andreev, Oleg A.
Date:
Type:
Articles
Department(s):
Pharmacology
Neurological Surgery
Volume:
110
Persistent URL:
Book/Journal Title:
Proceedings of the National Academy of Sciences of the United States of America
Abstract:
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.
Subject(s):
Cytology
Pharmacology
Neurosciences
Publisher DOI:
https://doi.org/10.1073/pnas.1220038110
Item views
253
Metadata:
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Suggested Citation:
Evgeny A. Sosunov, Evgeny P. Anyukhovsky, Alexander A. Sosunov, Anna Moshnikova, Dayanjali Wijesinghe, Donald M. Engelman, Yana K. Reshetnyak, Oleg A. Andreev, , pH (low) insertion peptide (pHLIP) targets ischemic myocardium, Columbia University Academic Commons, .

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