pH (Low) Insertion Peptide (pHLIP) Targets Ischemic Myocardium

Authors

Eugene A. Sosunov
Evgeny P. Anyukhovsky
Alexander A. Sosunov
Anna Moshnikova, University of Rhode IslandFollow
Dayanjali Wijesinghe
Donald M. Engelman
Yana K. Reshetnyak, University of Rhode IslandFollow
Oleg A. Andreev, University of Rhode IslandFollow

Document Type

Article

Date of Original Version

1-2-2013

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.

Citation/Publisher Attribution

Sosunov, E. A., Anyukhovsky, E. P., Sosunov, A. A., Moshnikova, A., Wijesinghe, D., Engelmand,D. M., Reshetnyak, Y. K., & Andreev, O. A. (2013). pH (low) insertion peptide (pHLIP) targets ischemic myocardium. Proceedings of the National Academy of Sciences, 110(1), 82-86. doi: 10.1073/pnas.1220038110

Available at: http://dx.doi.org/10.1073/pnas.1220038110

Publisher Statement

Freely available online through the PNAS open access option. © 2013 by The National Academy of Sciences of the USA