Structural and Hemodynamic Changes Associated with Physiologic Heart Hypertrophy of Pregnancy are Reversed Postpartum

We have previously characterized pregnancy-induced physiological heart hypertrophy. Pregnancy is associated with ventricular hypertrophy and short-term systolic and diastolic dysfunction due to volume-overload. Here we investigated whether cardiac structural and hemodynamic changes associated with pregnancy are reversed postpartum. Female mice (3-4month, C57BL/6) were used in non-pregnant diestrus-stage (NP), late pregnant (LP), 1-day postpartum (PP1), or 7-days PP (PP7). Echocardiography and cardiac-catheterisation were performed to monitor cardiac-hemodynamics. RT-PCR was performed to determine vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP2) transcripts. Trichrome staining for cardiac fibrosis and CD31 immunostaining for cardiac angiogenesis were performed. A p<0.05 was considered significant. Values were mean±SE. LP was associated with heart hypertrophy (p<0.05 vs. NP) that was reversed 7-days PP (heart weight: NP=120±3, LP= 163±2, PP1= 145±2, PP7= 117±1 mg). Conversely, heart weight/body weight (hw/bw) ratio was decreased in LP (p<0.05 vs. NP) that was reversed in PP1 (hw/bw: NP=5.9±0.1, LP= 4.5±0.1, PP1= 5.6±0.1). LV ejection fraction was reduced in LP (p<0.05 vs. NP) and was also restored at PP1 (NP=74±4, LP= 57±1, PP1= 73±1%). Cardiac angiogenesis was significantly increased in LP (p<0.001 vs. NP), and was fully restored in PP7 (p<0.001 vs. LP) (Capillary density: NP=0.95±0.01, LP=1.25±0.02, PP7=0.98±0.01 capillaries/myocyte). Similarly, VEGF was upregulated in LP, and was restored in PP7 (NP=1±0.1, LP=1.4 ±0.1, PP7=0.83±0.1). There was no increase in cardiac fibrosis in pregnancy-induced heart hypertrophy. Transcript levels of extracellular matrix (ECM) degrading enzyme MMP2 were downregulated in LP (p<0.05 vs. NP) and were restored at 7-days PP (NP=1±0.01, LP=0.47±0.03, PP7=0.70±0.1). In conclusion, pregnancy-induced heart hypertrophy is associated with increased cardiac angiogenesis, lack of fibrosis, decreased MMP2 and decreased diastolic function of the heart that are reversed postpartum. We speculate that physiologic heart hypertrophy of pregnancy has minimal cardiac ECM remodeling.