Pretreatment with TRV120023 significantly diminished cell death compared with losartan in mice subjected to acute cardiac injury, an effect dependent on β-arrestin-2.
Does TRV120023 reduce cell death in mice subjected to acute cardiac injury compared to losartan?
The β-arrestin-biased AT1R ligand TRV120023 provides cardioprotective benefits, including improved contractility and reduced cell death during acute cardiac injury, which are distinct from traditional ARBs like losartan.
Pharmacological blockade of the ANG II type 1 receptor (AT1R) is a common therapy for treatment of congestive heart failure and hypertension. Increasing evidence suggests that selective engagement of β-arrestin-mediated AT1R signaling, referred to as biased signaling, promotes cardioprotective signaling. Here, we tested the hypothesis that a β-arrestin-biased AT1R ligand TRV120023 would confer cardioprotection in response to acute cardiac injury compared with the traditional AT1R blocker (ARB), losartan. TRV120023 promotes cardiac contractility, assessed by pressure-volume loop analyses, while blocking the effects of endogenous ANG II. Compared with losartan, TRV120023 significantly activates MAPK and Akt signaling pathways. These hemodynamic and biochemical effects were lost in β-arrestin-2 knockout (KO) mice. In response to cardiac injury induced by ischemia reperfusion injury or mechanical stretch, pretreatment with TRV120023 significantly diminishes cell death compared with losartan, which did not appear to be cardioprotective. This cytoprotective effect was lost in β-arrestin-2 KO mice. The β-arrestin-biased AT1R ligand, TRV120023, has cardioprotective and functional properties in vivo, which are distinct from losartan. Our data suggest that this novel class of drugs may provide an advantage over conventional ARBs by supporting cardiac function and reducing cellular injury during acute cardiac injury.
Kim et al. (Sat,) conducted a other in Acute cardiac injury. TRV120023 vs. Losartan was evaluated on Cell death. Pretreatment with TRV120023 significantly diminished cell death compared with losartan in mice subjected to acute cardiac injury, an effect dependent on β-arrestin-2.