Figure 7.

Parp1 Loss of Function Confers Protection Against PAB-Induced RV Dysfunction

(A) Schematic of the experimental design. (B) CO, SV, TAPSE, and S′ wave measured using echocardiography in WT and Parp1-KO mice 7 weeks after PAB or sham surgery. (C) RV hypertrophy by Fulton index and relative mRNA levels of Nppa and Nppb expression in mice. (D) Representative images and quantification of Masson’s trichrome staining and relative mRNA levels of Col1α1 and Col3α1 expression in right ventricles from WT and Parp1-KO mice subjected to PAB or sham surgery. (E) Representative images of hematoxylin and eosin–stained RV sections and quantification of CSA. (F) Representative images and quantification of infiltrated macrophages stained with anti-CD68. Relative mRNA levels of Ccl2 and Socs3 in right ventricles of 7-week sham- or PAB-operated WT and Parp1-KO mice. (G) Representative images of TUNEL-stained RV sections and quantification of the percentage of positive cells. (H) Representative western blots and quantification of PARP1, pPKM2, PKM2, PKM1, phosphorylated signal transducer activator of transcription 3 (pSTAT3), STAT3, cMYC, hexokinase 2 (HK2), lactate dehydrogenase (LDH), and NUDT1 in right ventricles from WT and Parp1-KO mice subjected to PAB or sham surgery. Scale bars, 50 mm. Arrowheads, positive cells. WT sham, n = 3; Parp1-KO sham, n = 4; WT PAB, n = 11; and Parp1-KO, n = 10. Female mice are indicated by triangular symbols, and male mice are indicated by circular symbols. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001. Scatter dot plots show individual values and mean ± SEM. Comparisons were made using 1-way analysis of variance followed by Tukey multiple-comparison tests or nonparametric Kruskal-Wallis tests. Abbreviations as in Figures 1, 2, 5, and 6.