Fig. 4: Smac mimetic LCL161 reduces cardiac injury following MI.
From: Hematopoietic expression of cIAP2 drives inflammation and heart failure after myocardial infarction
Smac mimetic LCL161 is cardioprotective after MI. a, LCL161 stimulates degradation of cIAP1/2. b, In vivo cIAP1/2 degradation in spleen and heart tissues following dose titration of LCL161. Immunoblot representative of two similar experiments. c, Strategy for LCL161 administration following MI. d, Kaplan–Meier survival analysis of mice subjected to MI receiving vehicle or LCL161 gavage. Vehicle-treated controls, n = 18 mice (start of experiment); LCL161-treated controls, n = 15 mice (start of experiment). e, LV scar area of MI-operated mice receiving vehicle control (top) or LCL161 (10 mg kg−1, bottom); n = 7 per group. Scale bars, 1mm. f, Heart weight:tibia length D28 post-MI. g, LV end systolic diameter and measurements taken D28 post-MI. h, LV ejection fraction measured D28 post-MI. Control operated mice, n = 7 (3 LCL-treated, 4 vehicle treated); MI-operated mice, n = 10 vehicle treated, n = 11 LCL161-treated. i, Flow cytometry of heart infiltrating neutrophils, Ly6Chi monocytes and dendritic cells D28 post-MI. Control-operated mice, n = 3 (two vehicle-treated, one LCL161-treated); MI-operated mice, n = 6 per group. Data aggregate from three experiments (d–i). j, Quantitative PCR of remodeling gene products D28 post-MI; n = 4 per MI treatment group. Error bars denote mean ± s.d.; P values were calculated using Gehan-Breslow-Wilcoxon test (d), two-sided t-test (e,j), one-way ANOVA with Bonferroni’s correction (f,g,h,i). LCL, LCL161; LVESD, left ventricular end-systolic diameter; Veh, vehicle.
