Abstract P2019: Do Changes In Metabolism Or Lactation Mediate The Reversal Of Pregnancy-induced Cardiac Growth?

Abstract

During pregnancy, the maternal heart undergoes physiologic growth, which reverses following parturition and is associated with the restoration of hemodynamic parameters. However, the molecular processes underlying the reversal of pregnancy-induced cardiac growth and the time frame in which these changes occur remain unclear. Because changes in cardiac metabolism have been shown to influence the remodeling in the maternal heart, changes in metabolism may also contribute to the reversal of pregnancy-induced remodeling. Therefore, the goal of this study was to examine the underlying processes that contribute to the structural and functional changes occurring in the maternal heart following parturition. Timed pregnancy studies in 12-week-old female FVB/NJ mice showed that heart weight to tibia length (HW:TL) and cardiomyocyte size were highest in lactating 1-week post-birth (PB) mice versus mid-pregnant (8 d), late-pregnant (LP; 16 d), and non-pregnant (NP) mice. Interestingly, we also found that HW:TL was significantly reduced in non-lactating 1-week post-birth mice (PBNL) compared with LP mice. To determine the time-course of the reversal of pregnancy-induced remodeling and to examine the impact of lactation, we examined HW:TL in PB and PBNL mice 1, 3, and 6 weeks following parturition. We find that HW:TL is significantly higher in lactating PB mice versus non-lactating PBNL mice at 1 (8.71 ± 0.05 v 7.09 ± 0.26 mg/mm) and 3 weeks following parturition (8.90 ± 0.40 v 6.92 ± 0.56 mg/mm); however, 6 weeks after parturition, HW:TL was comparable between PB (7.35 ± 0.29 mg/mm) and PBNL groups (7.05 ± 0.18 mg/mm). Nevertheless, HW:TL remained elevated for 6 weeks after parturition in PB and PBNL mice compared with NP mice. RNA-Seq showed reductions in metabolic transcripts in PB hearts, including Pdk4 . Immunoblot analysis of key metabolic proteins showed that Pdk4 was reduced in hearts from 1 and 3 PB versus 1 and 3 weeks PBNL and NP. Together, these findings suggest that lactation influences the reversal of pregnancy-induced cardiac growth, which may be due in part to changes in cardiac metabolism.