Placental CRH and child cardiovascular disease risk and obesogenic eating behaviors

项目总结/摘要 心血管疾病（CVD）是美国死亡的主要原因，预计患病率将保持在 升中国CVD的起源开始于生命的早期，包括儿童肥胖和动脉粥样硬化斑块形成， 预测以后的CVD为了解决CVD的起源，美国心脏协会制定了2020年影响目标 强调促进生命早期的心血管健康，包括身体风险和 因素（例如，体重指数[BMI]，血压）和健康行为（例如，饮食）。产前压力 这一时期被认为是导致成年期CVD的原因。然而，对合理的生物学原理知之甚少。 机制等这项建议的重点是评估胎盘促肾上腺皮质激素释放激素的作用 (CRH)，一种未充分研究的应激反应激素，可调节胎儿发育和出生结果， 后代CVD风险（BMI z评分，腰围和血压）和致肥胖饮食行为。 本项目将采用纵向设计，前瞻性地跟踪一个样本的母子二人组（n = 150）。 作为NIMH资助的研究（R 01 MH 109662）的一部分，通过母体血液评估了胎盘CRH 在妊娠期间的三个时间点（10、24和34孕周）采集样本。儿童CVD风险（BMI z评分， 腰围，血压）和肥胖饮食行为正在评估的一部分， 儿童3岁时进行实验室访视时进行NHLBI资助的后续研究（R 01 HL 155744）。的 本项目有两个目的：目的1：检验胎盘CRH的快速增加是否与胎盘CRH的表达有关的假设。 妊娠期预测3岁时后代CVD风险更高;目标2：检验以下假设： 整个妊娠期胎盘CRH产生增加预示着后代更大的致肥胖饮食行为。 确定妊娠期胎盘CRH与后代CVD风险和 肥胖饮食行为将阐明心血管健康的早期起源，并提供早期治疗的目标。 预防和干预。在进行拟议的研究期间，申请人将在 丹佛大学，强烈支持她成为一个独立的NIH资助的研究人员的目标。的 申请人的目标包括：1）增加对产前期作为敏感期的理解， 产前应激生理学（例如，胎盘CRH）; 2）发展CVD风险评估的专业知识， 幼儿期; 3）发展幼儿期饮食行为评估的专业知识; 4）学习 纵向数据的高级统计建模;和5）发展赠款写作技能。完成这些 培训目标，沿着强大的导师从项目赞助商（Elysia戴维斯，博士）和合作， 导师（Jenalee Doom博士，Deborah Glueck博士，Julie Lumeng博士和Benjamin Hankin博士）将 支持申请人成为独立研究员的职业轨迹。

PROJECT SUMMARY/ABSTRACT Cardiovascular disease (CVD) is the leading cause of death in the US, with the prevalence projected to keep rising. The origins of CVD begin early in life, including child obesity and atherosclerotic plaque formation, which predict later CVD. To address the origins of CVD, the American Heart Association created 2020 Impact Goals emphasizing promotion of cardiovascular health early in life, which includes measures of both physical risk factors (e.g., body mass index [BMI], blood pressure) and health behavior (e.g., diet). Stress in the prenatal period is hypothesized to contribute to CVD in adulthood. However, little is known about plausible biological mechanisms. The focus of this proposal is to assess the role of placental corticotrophin-releasing hormone (CRH), an understudied stress responsive hormone that regulates fetal development and birth outcomes, in offspring CVD risk (BMI z-score, waist circumference, and blood pressure) and obesogenic eating behaviors. This project will utilize a longitudinal design to prospectively follow a sample of mother-child dyads (n = 150). Placental CRH was assessed as a part of a NIMH-funded study (R01MH109662) through maternal blood samples at three timepoints during pregnancy (10, 24, and 34 gestational weeks). Child CVD risk (BMI z-score, waist circumference, and blood pressure) and obesogenic eating behaviors are being assessed as a part of a follow-up NHLBI-funded study (R01HL155744) at a laboratory visit when the children are 3-years-old. The current project has two aims: Aim 1: To test the hypothesis that rapid increases in placental CRH across gestation predict greater offspring CVD risk at three years of age; and Aim 2: To test the hypothesis that increased placental CRH production across gestation predicts greater offspring obesogenic eating behaviors. Identifying the associations between placental CRH across gestation and both offspring CVD risk and obesogenic eating behaviors will elucidate early origins of cardiovascular health and provide targets for early prevention and intervention. While conducting the proposed study, the applicant will gain essential training at the University of Denver that strongly supports her goal of becoming an independent NIH-funded researcher. The applicant’s goals include 1) increasing understanding of the prenatal period as a sensitive period, focusing on prenatal stress physiology (e.g., placental CRH); 2) developing expertise in the assessment of CVD risk during early childhood; 3) developing expertise in the assessment of eating behaviors during early childhood; 4) learning advanced statistical modeling of longitudinal data; and 5) developing grant writing skills. The completion of these training objectives, along with the strong mentorship from the project sponsor (Elysia Davis, PhD) and co- mentors (Jenalee Doom, PhD, Deborah Glueck, PhD, Julie Lumeng, MD, and Benjamin Hankin, PhD), will support this applicant’s career trajectory toward becoming an independent researcher.