%0 Journal Article
%T Pepducin-mediated cardioprotection via ¦Â-arrestin-biased ¦Â2-adrenergic receptor-specific signaling
%A Claudio de Lucia
%A Douglas G. Tilley
%A Erhe Gao
%A Jeffrey L. Benovic
%A Laurel A. Grisanti
%A Rhonda L. Carter
%A Toby P. Thomas
%A Walter J. Koch
%J Theranostics
%D 2018
%I Ivyspring International Publisher
%R 10.7150/thno.26619
%X Reperfusion as a therapeutic intervention for acute myocardial infarction-induced cardiac injury itself induces further cardiomyocyte death. ¦Â-arrestin (¦Âarr)-biased ¦Â-adrenergic receptor (¦ÂAR) activation promotes survival signaling responses in vitro; thus, we hypothesize that this pathway can mitigate cardiomyocyte death at the time of reperfusion to better preserve function. However, a lack of efficacious ¦Âarr-biased orthosteric small molecules has prevented investigation into whether this pathway relays protection against ischemic injury in vivo. We recently demonstrated that the pepducin ICL1-9, a small lipidated peptide fragment designed from the first intracellular loop of ¦Â2AR, allosterically engaged pro-survival signaling cascades in a ¦Âarr-dependent manner in vitro. Thus, in this study we tested whether ICL1-9 relays cardioprotection against ischemia/reperfusion (I/R)-induced injury in vivo.
%K Pepducin
%K ¦Â-arrestin
%K ¦Â2-adrenergic receptor
%K cardiac ischemia/reperfusion
%K cardiomyocyte
%U http://www.thno.org/v08p4664.htm