Figure 2. Diminished 5-HT_2B signaling decreases fibrotic scar formation and border zone (BZ) expansion after myocardial infarction (MI) through alterations in collagen composition.

A-C, Analytical approach of calculating tissue thickness (A), demarcation of scar vs. healthy myocardium (B), and (C) mathematical definition of BZ as the transition region between scar dominated (>85% collagen stained red with picrosirius red; PSR) and myocardium dominated (>85% myocardium stained yellow) with inset illustrating a representative curve from each treatment. D, Thickness of the formed scar is decreased with SB204741 (SB) treatment but does not thin over time (N=3–10). E, Decreased BZ infiltration with 5-HT_2B antagonism as indicated by the rapid transition from scar to myocardium (N=8–10). F, No difference in interstitial fibrosis was observed (N=8–10). G-H, PSR stain imaged under polarized light in the BZ and scar revealed an increased proportion of thinner, less mature collagen fibers in the BZ of SB-treated mice (N=9–10). I, Analysis of collagen fiber orientation in the BZs of DMSO- (31 FOVs across 4 mice) and SB- (35 FOVs across 5 mice) treated animals to quantify the distribution of orientations to classify as isotropic or anisotropic. All data collected 6 weeks post-MI except where noted in D. D-F, H, Mean ± SEM, *P<0.05, **P<0.01 (color denotes difference between corresponding color proportion in H) (D,H) 2-way ANOVA and Holm-Sidak post hoc test or (E,F) 2-tailed Student t test.