Figure 9. Mechanisms of miR-145-mediated cardioprotective effects against MI. miR-145 promotes the expression of β2AR via activation of Akt/CREB cascades and enhances β2AR-Gi activity, which in turn restricts β1/2AR-Gs signaling and leads to reduced response to β-adrenergic stimuli. Furthermore, MI-induced hyperactivation of CaMKII promote RyR2-mediated Ca2+ release and result in activation of NCX1, which finally leads to delayed depolarization. At the meantime, CaMKII suppressed SERCA2a and Cav1.2 expression via HDAC4 and NF-κB (p65) pathway respectively, thus impair Ca2+ re-uptake, excitation-contraction coupling and cardiac performance. However, miR-145-mediated inhibition on CaMKII expression partially reversed the related disadvantages.