Figure 3.
Chronic catecholamine stimulation reversibly rescues contractile dysfunction without hypertrophy in CM-EGFR-KD mice. %EF (A) and %FS (B) of adult EGFRf/f (Cre−) or CM-EGFR-KD mice infused with vehicle or ISO (3 mg/kg/day) were monitored via echocardiography for up to 4 weeks. n = 7 EGFRf/f (Cre−) + Veh, EGFRf/f (Cre−) + ISO, and CM-EGFR-KD + Veh, n = 11 CM-EGFR-KD + ISO and n = 6 CM-EGFR-KD + ISO (2 weeks on/2 weeks off). **P < 0.01 CM-EGFR-KD + Veh vs. CM-EGFR-KD + ISO, †P < 0.05, ††P < 0.01 CM-EGFR-KD + Veh vs. CM-EGFR-KD + ISO (2 weeks on/2 weeks off), #P < 0.05, ###P < 0.001 EGFRf/f (Cre−) + Veh vs. CM-EGFR-KD + ISO, ‡‡‡P < 0.001 EGFRf/f (Cre−) + Veh vs. CM-EGFR-KD + ISO (2 weeks on/2 weeks off) at corresponding timepoints, ordinary two-way ANOVA with Bonferonni’s multiple comparisons test. (C) WGA staining of the LV of adult EGFRf/f (Cre−) vs. CM-EGFR-KD mice infused with vehicle or ISO for 2 (left) or 4 weeks (right). Panels shown are representative images from n = 6 [EGFRf/f (Cre−) Veh and ISO 2 weeks], n = 8 (CM-EGFR-KD Veh and ISO 2 weeks), n = 7 [EGFRf/f (Cre−) Veh and ISO 4 weeks] and n = 7 (CM-EGFR-KD Veh and ISO 4 weeks) mouse hearts; scale bars denote 100 µm. (D) Quantification of cardiomyocyte size from (C). ***P < 0.001, ordinary one-way ANOVA with Tukey’s multiple comparisons test. (E) βAR LV membrane density was measured in adult EGFRf/f (Cre−) vs. CM-EGFR-KD mice (n = 4 each) infused with vehicle or ISO for 4 weeks. ns, not significant, ordinary one-way ANOVA with Tukey’s multiple comparisons test.