Abstract Thu160: Cardiomyocyte Prolactin Signaling is Essential for Adaptation of the Heart to Pregnancy

Le résumé fourni par la source

Background: The heart adapts to pregnancy at transcriptional, metabolic, morphologic, and functional levels, ensuring that demands of both the mother and developing child are adequately met. How extra-cardiac signals coordinate cardiac adaptation to pregnancy is poorly understood. For various maternal tissues, including mammary glands, adipose and pancreatic β-cells, lactogenic hormones act via the prolactin receptor (PRLR) to orchestrate tissue adaptation during pregnancy. Objective: To determine whether cardiomyocyte prolactin signaling is required for cardiac adaptation to pregnancy. Approach: Timed pregnancies were performed in cardiomyocyte-specific PRLR knockout (cmPRLR-KO) and littermate control (CON) female mice at 9 weeks of age. Systolic and diastolic function were assessed by echocardiography at gestation day 16. Immediately following echocardiography, hearts were isolated for gravimetric, histologic, and molecular analyses. In a subset of studies, the impact of multiple (3) sequential pregnancies was investigated in cmPRLR-KO and CON mice. In all experiments, non-pregnant age-matched female mice were assessed in an identical manner. Results: As anticipated, a single pregnancy increased biventricular weight (+17%; p<0.001), cardiomyocyte size (+64%; p<0.001), left ventricular (LV) area (+8%; p=0.045), and cardiac output (+16%; p=0.032) in CON mice. In contrast, pregnancy-induced alterations in these parameters were either abolished or significantly (p<0.05) attenuated in cmPRLR-KO mice. Given impaired cardiac adaptation of cmPRLR-KO mice to a single pregnancy, we hypothesized that this may lead to maladaptation following multiple pregnancies. Consistent with this premise, 3 sequential pregnancies resulted in cardiomyopathy in cmPRLR-KO mice (but not in CON mice), characterized by reduced LV ejection fraction (-45%; p<0.001), increased LV volume (+196%; p<0.001), increased cardiomyocyte size (+69%; p=0.001), and induction of adverse cardiac remodeling markers (e.g., +266% nppa mRNA; p=0.002). Conclusions: Cardiomyocyte prolactin signaling is essential for adaptation of the heart to pregnancy. Loss of cardiomyocyte prolactin signaling precipitates cardiomyopathy following multiple pregnancies.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.