Research Paper Volume 12, Issue 12 pp 11603—11622

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-G_i activity, which in turn restricts β1/2AR-G_s 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 Ca_v1.2 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.