Abstract P1176: What Is The Nature Of The Hypertrophic Response Contributing To Pregnancy-induced Cardiac Growth And Its Reversal?

Abstract

During pregnancy, the maternal heart undergoes physiological cardiac growth, reversing following parturition; however, the contributing underlying processes are largely unknown. Changes in cardiac metabolism appear to be associated with cardiac growth through a reduction in glucose catabolism. We have also shown that several cardiac metabolic transcripts, proteins, and liver-derived metabolites that are elevated during pregnancy are associated with cardiac growth. However, the nature of the hypertrophic response observed in the maternal heart is unclear. Therefore, this study aimed to examine the metabolic and hypertrophic changes associated with pregnancy-induced cardiac growth and reversal. Studies revealed that both heart weight (HW: TL; p < 0.0001) and liver weight (LIV: TL; p <0.0001) were highest in lactating 1-week post-birth (PB) mice versus mid-pregnant (8 d), late-pregnant (LP; 16 d), and non-pregnant (NP) 12-week-old FVB/NJ mice. Of note, we also found that HW: TL ( p < 0.01) and LIV: TL ( p < 0.0001) were significantly reduced in non-lactating 1-week post-birth mice (PBNL) compared with PB mice. However, the changes in cardiac size observed during pregnancy and post-birth were not associated with changes in either cardiomyocyte cross-sectional area or cardiac fluid content. Hearts and livers remained significantly larger, irrespective of lactation status, following parturition through 6 weeks post birth (PB) versus NP. Consistent with these changes, we found significant reductions in Pdk4 protein between 1- and 3-week PB and PBNL groups that were reversed by six weeks postpartum and a substantial increase in Pdk4 expression at six weeks postpartum, respectively. Interestingly, we see a sustained increase in cardiac Bdh1 expression that persisted at six weeks postpartum, which could contribute to the sustained increases in HW: TL versus NP. Changes in lactation status and metabolism are likely contributing to similar patterns of growth seen in the heart and liver during and following pregnancy. The maternal hypertrophic response is considered eccentric due to the absence of changes in myocyte cross-sectional area and cardiac fluid content.