Inhibition of the Notch1 pathway induces peripartum cardiomyopathy

Figures

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  Figure 1. Inhibition of Notch1 induces and promotes postpartum ventricular dilatation. All data were presented as mean ± SD (n = 6). All the parameters were evaluated at 3 weeks post‐partum. A, LVEDD, left ventricular end‐diastolic diameter; B, LVEDV, left ventricular end‐diastolic volume; C, LVESD, left ventricular end‐systolic diameter; D, LVESV, left ventricular end‐systolic volume; E, LVPWT, left ventricular posterior wall thickness; F, IVST, interventricular septal thickness; G, LVEF, left ventricular ejection fraction; and H, LVFS, left ventricular fractional shortening. *P < .05 vs indicated group. Comparisons between groups were analysed by two‐way ANOVA with Bonferroni's post‐test

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  Figure 2. Inhibition of Notch1 increases serum cathepsin D and sFlt‐1 and promote cleavage of 23‐kD PRL to 16‐kD PRL. A, Serum cathepsin D was detected by ELISA. B, Serum sFlt‐1 was detected by ELISA. C, The cleavage of 23‐kD PRL to 16‐kD PRL in serum was determined by Western blot. All data were presented as mean ± SD (n = 6). *P < .05, *P < .05 vs indicated group. Comparisons between groups were analysed by two‐way ANOVA with Bonferroni's post‐test

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  Figure 3. Inhibition of Notch1 promotes myocardial hypertrophy and interstitial fibrosis in the left ventricle. A, The ration of heart weight/bodyweight, HW/BW. B, The ratio of heart weight/tibia length, HW/TL. C, Haematoxylin‐eosin was used to evaluate the ventricular wall thickness and cavity. D, Masson's trichrome staining was used to evaluate the fibrosis. E, Wheat germ agglutinin staining was used to analyse the cardiomyocyte surface area. F, The relative expression of ANP, BNP, β‐MHC and COL1A1 mRNA was evaluated by real‐time PCR. All data were presented as mean ± SD (n = 6). *P < .05, **P < .01 versus indicated group. Comparisons between groups were analysed by two‐way ANOVA with Bonferroni's post‐test

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  Figure 4. Inhibition of Notch1 suppresses postpartum myocardial angiogenesis. A‐C, The relative expression of VEGFA, PDGFB and BFGF mRNA in LV tissues was evaluated by real‐time PCR. D, The relative expression of VEGFA, PDGFB and BFGF protein in LV tissues was evaluated by Western blot. E, The micro‐vessel density as indicated by CD31 IHC staining. All data were presented as mean ± SD (n = 6). *P < .05 versus indicated group. Comparisons between groups were analysed by two‐way ANOVA with Bonferroni's post‐test

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  Figure 5. Inhibition of Notch1 decreases N1ICD, Hes1, and p‐Stat3 and increases cathepsin D in left ventricle tissue. All data were presented as mean ± SD (n = 6). The relative expression of N1ICD, Hes1, p‐Stat3 and cathepsin D protein was evaluated by Western blot. *P < .05, *P < .05 vs indicated group. Comparisons between groups were analysed by two‐way ANOVA with Bonferroni's post‐test