Figure 9. A flow-chart showing the putative mechanism for the deteriorated cardiac function by HRC-KD in TAC-HF model.

Down-regulation of HRC expression induces increased RyR2 and SERCA2 activities followed by an increase of cytosolic Ca²⁺, which leads to activation of CaMKII and increased mitochondrial Ca²⁺ uptake. The activated CaMKII phosphorylates downstream kinases and causes cardiac cell death through an imbalance of the Bax/Bcl-2 ratio.