Calcium overload induces Ca2+ binding to CaMKII in order to promote phosphorylation of CaMKII and CREB (Figure 3(b)); simultaneously, the expressions of ERS regulatory proteins, GRP78 and Caspase-12, were both increased in HF rats (Figure 3(c)), implying that ERS can cause SERCA2a degradation and cardiac diastolic dysfunction. This evidence concerns the gene CASP12 and hydrops fetalis.