Fig. 5: Pro-resolving therapy to mitigate cardiac disease onset in juvenile D2-mdx.

A Schematic describing the inflammatory response following cardiac injury in health (black trace) or dystrophic (red trace), showing acute versus chronic inflammation respectively. Use of anti-inflammatory drug (purple trace) lowers inflammatory response blunting inflammation, instead use of pro-resolving therapy (green trace) does not impact the onset of inflammation but helps clear inflammation preventing the inflammation to become chronic. B Schematic detailing the pre-clinical testing of pro-resolving drug, BMS-986235 (6.0 mg/kg, 3 wk daily administration) in D2-mdx mice (n  ≧6) just prior to disease onset (18-19 days old). C Whole tissue images of the matched orientation of hearts showing ventricular and atrial fibro-calcified damage in saline or BMS-986235-treated D2-mdx mice. D Image showing cross-section of D2-mdx heart stained for histological features by H&E from mice treated with saline or BMS-986235. E Images showing cross-section of D2-mdx heart immunostained for pan-macrophage marker, F4/80 (red) and counterstained with WGA (green) and DAPI (blue) to mark the ECM and nuclei, respectively. F Image showing heart cross-section immunostained for COL1A1 and counterstained with DAPI (blue) to visualize nuclei. G, H qRT-PCR analysis of inflammatory (G) and extracellular matrix genes (H) to assess the effect of drug treatment of D2-mdx mice (red triangles), as compared with saline-treated controls (black triangles). Relative gene expression values normalized to internal Hprt transcript levels. Data represent median ± IQR from n  ≧6 hearts per cohort. Statistical analyses performed using non-parametric Mann–Whitney test; *p < 0.05, **p < 0.01, ***p < 0.001.