Figure 6: Anti-TNF antibody treatment normalizes CM hypertrophy in vivo. | Nature Communications

Figure 6: Anti-TNF antibody treatment normalizes CM hypertrophy in vivo.

From: Cellular interplay via cytokine hierarchy causes pathological cardiac hypertrophy in RAF1-mutant Noonan syndrome

Figure 6

(a) Schematic of the treatment regimen. (b) TNF inhibition normalizes LVPWd after treatment for 6 weeks, as assessed by echocardiography (mean±s.e.m.; n=10 (Tie2-control+IgG isotype control), 11 (Tie2-control+anti-TNF Ab), 7 (Tie2-L613V+IgG isotype control) or 9 (Tie2-L613V+anti-TNF Ab); **P<0.005, Bonferroni’s post-test when ANOVA was significant; #P<0.05 two-tailed Student’s t-test). (c) Representative WGA-stained cross-sections of hearts from treated animals (original magnification, × 200; scale bars, 50 μm). CSA (right), quantified using ImageJ (mean±s.e.m.; n=7 (Tie2-control+IgG isotype control), 9 (Tie2-control+anti-TNF Ab), 7 (Tie2-L613V+IgG isotype control) or 5 (Tie2-L613V+anti-TNF Ab); with 200 CMs counted per sample; *P<0.05, Bonferroni’s post-test when ANOVA was significant; #P<0.05, two-tailed Student’s t-test). (d) Ejection fraction and (e) fractional shortening, measured by echocardiography, showing preserved cardiac function following TNF inhibition (mean±s.e.m.; n=13 (Tie2-control+IgG isotype control), 15 (Tie2-control+anti-TNF Ab), 9 (Tie2-L613V+IgG isotype control) or 12 (Tie2-L613V+anti-TNF Ab); statistical significance was assessed using ANOVA). (f) Models illustrating how the combined cell-autonomous and non-cell-autonomous actions of activating RAF1 mutants cause NS-cardiomyopathy (see text for details).

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