Fig. 1: cIAP2 promotes injury following myocardial infarction.

cIAP2 is upregulated and participates during cardiac injury after MI. a, SOMAscan measurement of cIAP2, Survivin (BIRC5), cardiac Troponin T (cTNT) and N-Terminal pro-B-type Natriuretic Peptide (NT-proBNP) plasma protein samples from acute heart failure patients (n = 7 measured at admission and D3 and D30 post-admission) and healthy controls (n = 10). b, ELISA of serum cIAP2 from percutaneous coronary intervention patients. Acute MI (n = 9) and CAD (n = 12). c, Immunoblot of human heart tissue lysates probed for IAP proteins cIAP2, cIAP1 and XIAP from healthy or ischemic cardiomyopathy patients. Vinculin was probed as an expression control. d, Immunoblot of cIAP1 and 2 isolated from mouse LV tissue lysates D1, D3 and D7 post-MI. β-tubulin served as an expression control. Immunoblot representative of two experiments. e, Masson’s trichrome stained mouse midventricular heart sections (5 μm thickness) D28 post-MI. Left: wildtype C57Bl/6J (n = 7). Middle: CIap1^−/− (n = 6). Right: CIap2^−/− (n =7). Scale bars, 1 mm. LV scar area (collagen area − stained blue); morphometry of two representative slices per animal. f, Capillary density estimated by number of isolectin B4-positive (green) structures counted in LV MI border zone. Nuclei (DAPI) stained blue. Scale bars, 50 μm (n = 4 per treatment group). g, LV ejection fraction 28 days post-MI presented as % reduction from baseline (pre-MI) echocardiographic measurement. WT, n = 10; CIap1^−/−, n = 6; CIap2^−/−, n = 10. h, Heart and lung weights normalized to tibia length measured 4 weeks post-MI. Cont, n = 6 (WT), 4 (CIap1^−/−) and 5 (CIap2^−/−); MI-treated, n = 15 (WT), 10 (CIap1^−/−) and 10 (CIap2^−/−). i, Female mice: LV Ejection fraction. Left: WT (n = 8), CIap2^−/− (n = 7). Middle: heart weight:tibia length; sham-operated control WT (n = 3), CIap2^−/− (n = 3); MI, WT (n = 7), CIap2^−/− (n = 7). Right: lung weight:tibia length; sham-operated control WT (n = 3), CIap2^−/− (n = 3); MI WT (n = 7), CIap2^−/− (n = 7). j, LV MI border zone cell death (TUNEL-positive (red) staining) in 400× magnified 5 μm heart sections. Nuclei (DAPI) stained blue. Triplicate fields counted per study specimen. Scale bar, 50 μm; n = 8 (WT MI) and 7 (CIap2^−/− MI), respectively. Mouse data are aggregate from three experiments (male studies) or two experiments (female studies), respectively. Error bars, mean ± standard deviation (s.d.); P values were calculated using two-sided t-test (b,f,j), one-way ANOVA with Dunnett’s post-hoc test (a), one-way ANOVA with Bonferroni’s correction (e) and two-way ANOVA with Bonferroni’s correction (g,h,i). RFU, relative fluorescent units; Cont, control; D, day; HF, heart failure; ICM, ischemic cardiomyopathy; LV, left ventricular.

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