title: pH (low) insertion peptide (pHLIP) targets ischemic myocardium.
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.
authors.affiliation: Department of Pharmacology, Columbia University, New York, NY 10032, USA.
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Sosunov
authors.forename: Evgeny P
authors.initials: EP
authors.lastname: Anyukhovsky
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Sosunov
authors.forename: Anna
authors.initials: A
authors.lastname: Moshnikova
authors.forename: Dayanjali
authors.initials: D
authors.lastname: Wijesinghe
authors.forename: Donald M
authors.initials: DM
authors.lastname: Engelman
authors.forename: Yana K
authors.initials: YK
authors.lastname: Reshetnyak
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Andreev
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D005453:Fluorescence; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000008:administration & dosage; D008297:Male; D008565:Membrane Proteins / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*
chemical_list: D008081:Liposomes; D008565:Membrane Proteins; C533201:pHLIP protein