Excessive hypercholesterolemia in pregnancy alters maternal cardiac remodeling during pregnancy and postpartum

Excessive hypercholesterolemia (eHC) in pregnancy is associated with complications such as preeclampsia, yet its impact on maternal cardiac adaptation and long-term cardiovascular health remains unclear. We hypothesized that eHC impairs maternal cardiac structure and function during pregnancy and that these effects persist postpartum. Sprague Dawley rats were fed either a control diet (CTL) or high cholesterol diet (eHC) from gestational day (GD) 6-20 (term=22 days). Echocardiography was performed before pregnancy, at GD20, and 3 months postpartum. Plasma and left ventricular tissue were collected at GD20 and postpartum for molecular analyses. CTL dams demonstrated normal pregnancy-associated cardiac adaptations, including increased diastolic left ventricular internal diameter, stroke volume, cardiac output, and diastolic left ventricular volume in late pregnancy, with normalization postpartum. These adaptations were attenuated in eHC dams. In late pregnancy, eHC dams exhibited reduced stroke volume and cardiac output compared with CTL, along with alterations in diastolic function, including reduced mitral valve A' velocity. Postpartum, eHC dams showed changes in diastolic indices, including reduced mitral valve A-wave velocity and E'/A' ratio. Measures of systolic performance (ejection fraction and fractional shortening) were unchanged between groups. Molecular analyses revealed increased cardiomyocyte size, altered collagen remodeling characterized by an increased COL1-to-COL3 ratio, and elevated CD31 expression in eHC dams during pregnancy. Postpartum, collagen remodeling was evident, but now with reduced COL1 and increased COL3 expression. Together, these findings demonstrate that eHC disrupts normal maternal cardiac adaptation during pregnancy and promotes adverse remodeling and cardiac dysfunction postpartum, with potential implications for long-term cardiovascular disease risk.