Figure 7. GRK5 promotes dissociation of cardiac SAP97-β₁AR complex and β₁AR-CaMKII signaling in heart failure.

A-B) Cardiac expression of β₁AR, SAP97, PDE4D, PDE4B, GRK2 and GRK5 were detected in human heart tissues from healthy subjects and HF with either ischemic cardiomyopathy or dilated cardiomyopathy. * p < 0.05 by one-way ANOVA followed by Tukey’s test. C) The β₁AR was pulled down from human heart lysates from healthy and HF subjects. The pulled down β₁AR and SAP97 were detected by western blot. D) GRK2-cKO, GRK5-cKO and flox control mice were subjected to I.P. injection with isoproterenol (2 mg/kg) for 10 mins. The cardiac β₁AR was pulled down from heart lysates; and both β₁AR and SAP97 were detected in western blots. E) GRK5-f/f and GRK5-cKO mice were subjected to chronic infusion of isoproterenol (60 mg/kg/day) for 1 week. Cardiac fractional shortening was monitored with echocardiogram after isoproterenol infusion. ** p < 0.01 by one-way ANOVA followed by Tukey’s test. F) Total and phosphorylated CaMKII in GRK5-f/f and GRK5-cKO hearts after one-week infusion of isoproterenol were detected in western blot and quantified. ** p < 0.01 by unpaired t-test. G) Cartoon depicts the β₁AR signaling in healthy (SAP97-f/f) and failing (SAP97-cKO) hearts.