Abstract 956: Alterations in Cardiac Infiltration Accompany Peripartum Cardiomyopathy in a Transgenic Model
Introduction Peripartum cardiomyopathy (PPCM) is a rare cardiomyopathy of unknown etiology. An autoimmune process has been suggested as pregnancy occurs with immune function adaptations. Transgenic mice with cardiac-specific expression of TNFα (TNF1.6) develop dilated cardiomyopathy in virgin 40 week (wk) old females. However, 12 wk females develop heart failure and die (~25%) between postpartum (PP) day 12–28. We hypothesized that altered immune processes accompany PPCM and would be evidenced by changes in cardiac infiltrating cells and deposition of IgG.
Methods Four groups (n=7–12 each) were studied; ~12 wk old wild type (W) and TNF1.6 (Tg) mice which were either PP day 14 (PP) or virgins (V). Conductance catheter studies were performed on PP14 (or age-matched virgins), with cardiac tissues harvested for immunofluorescent (IF) microscopy (CD45+ all infiltrating; CD4+, CD8+, T-cells; CD19 B-cells; F4/80 macrophages; reported as % + cells, ~3000 cells per mouse), IgG deposition (% fractional area by IF), and apoptosis (% TUNEL+). Data reported as mean ± sem. ANOVA with posthoc identified significant differences between groups.
Results TgPP had greater (p<0.002) cardiac mass/tibial length (85.7±6.2 mg/cm) relative to WTV (47.7±2), WTPP (63.9±4), or TgV (52.6± 1). TgPP had decreased (p<0.003) EF (39.2±2%) relative to WTV (62.3±3), WTPP (65.4±4), or TgV (56.3±3). TgPP had increased (p<0.001) LV diastolic (VeD, 33.9±2 μl) and systolic (not shown) volumes relative to WTV (20.5±1), WTPP (21.3±1), or TgV (19.6±2). TgPP had increased (p<0.001) IgG deposition (16.2±2%) relative to all other groups (ranged from 0.8 to 1.44%). TgV had increased (p<0.03) CD4+, CD8+, and B-cell infiltrates relative to either WTV or WTPP, with unchanged macrophage levels (data not shown). However, TgPP had a decreased (p<0.001) CD8+ T-cells (0.6±0.1%) relative to TgV (1.6±0.1%), and increased (p<0.001) macrophages (14.6±1%) relative to TgV (2.7±1%), WTV (1.8±0.5%), or WTPP (3.2±1%). TgPP had significantly decreased TUNEL+ nuclei relative to TgV (data not shown).
Conclusions This model develops PPCM with altered cardiac infiltration and IgG deposition. Pregnancy associated-alterations in immune processes may induce PPCM in mice with pre-pregnancy cardiac inflammation.