Fig. 5: Long-term effects of GREM1/2 blockade.
a, Survival of TCRM mice after treatment with GREM1/2-neutralizing antibody (14-D10-2) or IgG2b isotype control antibody. b–d, Cardiac gross pathology (b), representative H&E-stained heart sections (c) and histopathological disease severity (d) of 20-week-old TCRM mice subjected to the indicated treatment (n = 9 and 10 mice per group). e, Dot plots depicting the average expression of the indicated genes in total cardiac cells (top) and cardiac fibroblasts (FB; bottom) of 12-week-old TCRM mice treated with the indicated antibodies. f, Top significantly enriched pathways according to GO enrichment analysis based on differentially expressed genes in all cardiac cells from TCRM mice treated with control or GREM1/2-neutralizing antibodies. g,h, Representative images of picrosirius red-stained heart sections (representative image from eight mice per group) (g) and quantification of collagen network size (h) from 12-week-old TCRM mice treated with control or GREM1/2-neutralizing antibodies (n = 8 mice per group from three independent experiments). i, Ejection fraction (EF) as determined by echocardiography in 8-week-old TCRM mice treated with 14-D10-2 or isotype antibody between week 4 and week 8. Numbers indicate fraction of mice developing heart failure before the end of the treatment period; box plots as in Fig. 1 (n = 18 and 21 mice per group). scRNA-seq and snRNA-seq data represent a total of 27,160 cells per nuclei from control (n = 4) and TCRM (n = 4) mice (e,f). Statistical analysis was performed using Mann–Whitney U-test (d,h,i) with **P < 0.01 and ***P < 0.001. ROS, reactive oxygen species.
