Figure 6.

Cardioprotective Effects of PARP1 and PKM2 Modulators in Rats Subjected to PAB

(A) Schematic representation of the experimental protocol for induction and therapeutic intervention in a PAB-induced RV dysfunction model in rats. (B) Pressure gradient (PG) at PAB site, SV, CO, tricuspid annular plane systolic excursion (TAPSE), S′ wave, RV fractional area change (FAC), and systolic and diastolic eccentricity index (EI) measured using echocardiography in PAB rats before and every week after treatment or not with olaparib or TEPP-46. (C) Representative echocardiographic images of the right and left ventricles obtained from a parasternal short-axis view in PAB rats treated with olaparib, TEPP-46, or Veh at 5 weeks after the initiation of the treatment. (D) RV systolic pressure (RVSP), CO, SV, and RV end-diastolic pressure (RVEDP) measured using right heart catheterization (RHC) at the end of the protocol in PAB rats treated or not with olaparib or TEPP-46. (E) RV hypertrophy by Fulton index and relative messenger RNA (mRNA) levels of Nppa and Nppb expression in PAB rats treated or not with olaparib or TEPP-46. (F) Representative images and corresponding quantifications of CD68, TUNEL, and Masson’s trichrome (Tri.) staining in RV sections from PAB rats treated or not with olaparib or TEPP-46. (G) Relative mRNA levels of Ccl2, IL-8, Socs3, Col1α1, and Col3α1 in PAB rats treated or not with olaparib or TEPP-46. (H) Representative western blots and quantification of PARP1, pPKM2, PKM2, PKM1, Nudix hydrolase 1 (NUDT1), and cMYC in right ventricles from PAB rats exposed or not to olaparib or TEPP-46. Scale bars, 25 mm. Arrows denote positive cells. n = 7 to 12 per group. ∗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. i.p = intraperitoneal; LV = left ventricle; other abbreviations as in Figures 1 and 2.