Figure 5.

Cilengitide reduces cardiac fibrosis and improves cardiac function after MI. (A) Design of the in vitro experiments to test the ability of isolated PW1⁺CD51⁺ cardiac cells to activate latent TGFβ. (B) TGFβ levels in isolated PW1⁺CD51⁺ cardiac cells supplemented with latent TGFβ and treated with or without the anti-integrin drug cilengitide (10 µM final concentration). Results are normalized to absolute values measured in vehicle-treated group. N = 9 from three independent isolates. ****P < 0.0001 using Mann–Whitney test between groups. (C) Experimental design: Mice were pre-treated for 7 days with cilengitide or vehicle (N = 16 per groups) before MI induction (Day 0) and then treated for 7 additional days. (D) Survival curves of cilengitide- and vehicle-treated mice 7 days after MI. *P < 0.05, log-rank test. (E) Left ventricular ejection fractions of cilengitide- and vehicle-treated mice immediately before surgery and 7 days later. **P < 0.01, ****P < 0.0001. (F) Analysis of infarct size and cardiac fibrosis between cilengitide- and vehicle-treated mice 7 days after MI was performed at 8 levels below the LAD ligation site. (G) Masson trichome staining in vehicle- and cilengitide-treated animals and quantification of infarct size and scar thickness between both groups, ***P < 0.001 (N = 4 per group). (H) Sirius red staining in vehicle- and cilengitide-treated animals and quantification of interstitial fibrosis in remote areas between both groups, ****P < 0.0001, (N = 4 per group). Data are mean ± SD. Drawings are from servier medical art (https://smart.servier.com) which is licenced under a creative commons attribution 3.0 unported license.