Mice (WT, PARP1+/-, and PARP1-/-) were infected with T. cruzi, and sacrificed at 150 days’ pi. (A-E) Cardiac structural changes were analyzed by echocardiography using a Vevo 2100 System. Shown are left ventricular (LV) mass (A), and systolic (-s) and diastolic (-d) changes in the thickness of the interventricular septum (IVS, B&C) and LV posterior wall (LVPW, D&E) in chronically infected and matched control mice (n = 8–12 mice/group, triplicate recordings per mouse). (F-H) Hearts were sectioned for various experiments as shown in G. Apex heart sections were stained with Mason’s trichrome, and representative images are shown in H.a-f. Tissue sections were scored for collagen (F, n = 4 mice/group, 2 slides per mouse, 10 microscopic fields per slide) as described in Materials and Methods. (I-K) Real time RT-qPCR analysis of myocardial levels of mRNAs for collagen isoforms COLI, COLIII, and COLV, in chronically infected (and control) WT, PARP1+/-, and PARP1-/- mice (n ? 5 mice/group, triplicate observations per mouse). Data were normalized to GAPDH mRNA. Data in all bar graphs are plotted as mean value ± SEM, and statistical significance are marked as *WT.Tc vs. WT, &genetically modified/infected vs. matched controls, and #WT.Tc vs. genetically-modified/infected (*,&,#p<0.05, **,##p<0.01, ***p<0.001).
The indices of LV systolic function, i.e., stroke volume (SV), cardiac output (CO), and ejection fraction (EF), were decreased by 66%, 51% and 46% respectively, in WT.Tc (vs. WT) mice (Fig 7A–7C, all, p<0.01). The systolic dysfunction prolonged the pre-ejection isovolumic contraction time (IVCT, 74% increase, Fig 7D, p<0.05) and shortened the LV ejection time (LVET, Fig 7E, p<0.05) in chagasic mice. Further, 40–67% changes in the early (E) and late (A) diastolic filling velocities indicated diastolic dysfunction in chagasic WT mice (Fig 7F & 7G, all, p<0.05). Both systolic and diastolic dysfunction contribute to abnormality in myocardial relaxation that was presented by 50% increase in isovolumic relaxation time (IVRT, Fig 7H, p<0.05) in WT.Tc mice. In comparison to WT.Tc mice, PARP1+/-.Tc and PARP1-/-.Tc mice exhibited a partial-to-full control of systolic and diastolic dysfunction, and myocardial contraction and relaxation indices, the maximal benefits of PARP1 deletion being observed in PARP1-/- mice (Fig 7A–7H).. ..