Figure 1
From: Mice with RyR1 mutation (Y524S) undergo hypermetabolic response to simvastatin
An acute dose of simvastatin at 32°C results in higher peak VO 2 levels in YS compared to WT mice. (A) IP injection of simvastatin triggers significantly higher peak VO2 values at 60 mg/kg (P < 0.05) and 80 mg/kg (P <0.001) compared to vehicle-only injection. (B) Curve-fit of increasing simvastatin doses in YS mice. (C) Pre-treatment with 600 mg/kg AICAR results in significantly (P < 0.01) lower peak VO2 values when administered 20 minutes after simvastatin treatment in YS mice. (D) Representative VO2 tracings of YS mice receiving 80 mg/kg of simvastatin show increasingly higher VO2 values than YS mice treated with both 80 mg/kg simvastatin and 600 mg/kg AICAR, vehicle-only (DMSO), or WT mice treated with 80 mg/kg simvastatin. AICAR, 5-aminoimidazole-4-carboxamide ribonucleoside; DMSO, dimethyl sulfoxide; VO2, oxygen consumption; WT, wild type; YS, Y524S.