The finding of this work can attribute to a better understanding of the ECM stiffness impact on the progress and treatment of DCM and also emphasizing the physiological effect of ECM stiffness on the drug efficacy in clinically treating DCM with proposing that the AT1R-FAK-NOX2 signaling pathway can be a new target for intervention of ECM stiffness in DCM. Here, AGTR1 is linked to familial dilated cardiomyopathy.