Our previous studies have demonstrated that activated membrane-bound IGF-IIR recruits Gαq to induce caspase-3-dependent apoptosis in response to injuries leading to the progression of heart failure, such as spontaneous hypertension-induced and abdominal aorta ligation-induced cardiac injury.14, 16 Therefore, we attempted to clarify whether IGF-IIR was implicated in zDOX-induced heart failure. Here, CASP3 is linked to hypertensive disorder.