Preserved Cardiac Contractility and Venous Return in Beta-arrestin2 Transgenic Mice During Sepsis With Insufficient Resuscitation

β-arrestin 2 is a negative regulator of inflammation and a protective signaling transducer in acute heart injury. In this study, using echocardiography and Millar Pressure-Volume systems, we found that heart dysfunction accompanied with hemodynamic instability occurred rapidly after experimental sepsis with insufficient resuscitation in wild type and β-arrestin 2 knock out mice but not in β-arrestin 2 transgenic mice. β-arrestin 2 overexpression is associated with preserved preload, cardiac output, systolic contractility and diastolic elasticity after cecal ligation and puncture (CLP). Furthermore, β-arrestin 2 overexpression up-regulated IL-6/IL-6R/gp130/STAT3 anti-apoptotic signaling through suppressing p38 activation and subsequently inhibiting phosphorylation of membrane bound gp130, the signal transducer part of IL-6 receptor complex. In conclusion, β-arrestin 2 is a crucial cardiac function regulator in sepsis.