Abstract 16482: Cardiac Remodeling During Pregnancy With Challenge: A Prologue of Pathological Remodeling

Abstract

Introduction: Life-style changes in the past decades have led to an increased incidence of metabolic syndrome (MetS), obesity and hypertension in women of childbearing age. These comorbidities are known to predispose individuals to adverse cardiovascular events. There is also evidence that cardiovascular complications during pregnancy may link to future heart diseases. During normal pregnancy, the heart undergoes physiological hypertrophy without fibrosis or fetal gene activation. However, recent study showed extremely obese women have increased cardiac hypertrophy and more frequent diastolic dysfunction at term. The objective of this research was to determine if MetS modifies the cardiac remodeling that takes place during pregnancy. Hypothesis: MetS during pregnancy induces pathological rather than physiological cardiac remodeling. Methods and Results: We performed long-term feeding of high fat (45%kcal) diet (HFD) in C57BL/6J female mice to establish a model of MetS, which showed increased body weight, impaired glucose tolerance and dyslipidemia compared to normal chow, resembling the features of human MetS. After pregnancy, HFD fed mice showed higher heart weight and ECHO-derived LV mass compared with Ctrl. Pregnant mice with MetS had signs of pathological cardiac remodeling, such as cardiomyocyte hypertrophy, fetal gene activation and interstitial fibrosis. At the transcriptome level, pregnancy in HFD fed mice lead to distinct gene expression patterns compared to normal pregnancy, with enrichment in genes involved in cardiac hypertrophy, oxidative stress and fibroblast activation that likely underly the adverse remodeling. Moreover, when animals were stressed with Angiotensin/phenylephrine infusion, MetS postpartum hearts had more severe cardiac hypertrophy, with overt concentric remodeling and increased fibrosis accumulation compared with nulliparous females Conclusions: MetS can induce maladaptive cardiac remodeling during pregnancy and exacerbate pathological remodeling in the postpartum heart.