Figure 6

Cardiac CX3CL1 or CX3CR1 knockdown at the onset of ECH, via intramyocardial siRNA injection, reverses iso-induced concentric hypertrophy and favors alteration of function and dilation. (A,D) Schematic representation of the protocol where mice implanted with an iso-pump at day 0 were subjected to a unique ultrasound-guided intramyocardial transthoracic injection of Scramble, Cx3cl1 or Cx3cr1 siRNAs at day 7. (B,E) Echocardiographic parameters measured at d0, d7, d12, d15, d22 and d28 concerning siScramble or siCx3cl1 injections; n = 5–13 mice/group. Measurement at d0, d7, d12 and d15 for siScramble or siCx3cr1 injections; n = 10–14 mice/group, two-way ANOVA followed by Sidak’s post-hoc tests; * p < 0.05, ** p < 0.01 vs scramble at the same time point. (C,F) Efficient knockdown of CX3CL1 or CX3CR1 protein levels in cardiac homogenates at d12, d15 and d28 following siRNA injection. Full unedited gels are in the supplementary material as well as detailed procedure (Figure S12 and S13). Mean ± SEM of mice, n = 4–6 mice/group, Kruskal–Wallis followed by Dunn’s post-hoc tests; * p < 0.05, ** p < 0.01.