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| Selective β-Arrestin Biased Agonist; TRV120023 Induced Cardioprotective Effects After Ischemia Reperfusion Injury |
| 제주대학교병원¹ , Depart. of Medicine, Cell Biology & Molecular Genetics, Duke University Medical Center² |
| 김기석¹ , 김송이¹ , 주승재¹ , Dennis Abraham² , Howard A. Rckman² |
Angiotensin type 1 receptor (AT1R) is one of the G protein coupled receptor (GPCR) superfamily and play crucial role in cardiac disease. In recent concept of AT1R signaling, β-arrestin 2-biased agonism is selective activation β-arrestin 2 rather than G protein, in which contributed cardioprotective effect during cellular injury. The cardioprotective effect has not been clearly investigated in animal model. Here, we shown that selective β-arrestin 2 biased agonist; TRV120023 enhanced cardiac performance and activated cardioprotective signal (ERK and Akt) in ischemia reperfusion (IR) injury mouse model. TRV120023 was also attenuated IR injury induced cadiomyocyte apoptosis. All of these effects are completely abolished in β-arrestin 2-knockout mouse and pretreatment of losartan (unbiased ligand, angiotensin receptor blocker) groups. These data demonstrated that TRV120023 played cardioprotective effect during cardiac IR injury and these effects were mediated by β-arrestin 2-biased agonism of AT1R.
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