Lactation, Oxytocin and Maternal Cardiovascular Function.

哺乳期、催产素和母亲心血管功能。

基本信息

批准号：
10774048
负责人：
Egle Bytautiene Prewit
金额：
$ 9.42万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10774048
关键词：
ADP-ribosyl Cyclase Adipose tissue Affect Age Behavior Birth Blood Pressure Blood Vessels Body Weight Bottle feeding Brain Brain region Breast Feeding Cardiac Cardiometabolic Disease Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cause of Death Cerebellum Child Health Chronic Disease Development Diastolic blood pressure Discipline of Nursing EFRAC Echocardiography Elderly Enterobacteria phage P1 Cre recombinase Epigenetic Process Event Exposure to Feedback Foundations Functional disorder Future Gender Gene Expression Goals Health Heart High Fat Diet Hour Human Hypertension Hypothalamic structure In Vitro Infant Intervention Knockout Mice Lactation Life Link Long-Term Effects Low-Density Lipoproteins LoxP-flanked allele Maternal Health Measures Mediating Messenger RNA Metabolic Metabolic syndrome Milk Milk Ejection Modeling Mothers Mus Neurons Neuropeptides Newborn Infant Nipples Obesity Observational Study Operative Surgical Procedures Organ Outcome Output Oxytocin Oxytocin Receptor Pattern Peripheral Phenotype Physiological Plasma Play Postpartum Period Pregnancy Procedures Production Prosencephalon Reflex action Regulation Reporting Risk Marker Role Social Behavior Stroke Volume System Testing Therapeutic Time Translating Uterine Contraction Visceral Woman Women&apos s Health antagonist blood pressure reduction cardioprotection conditional knockout design fasting glucose heart function improved in vivo lactation period magnocellular men micrography novel offspring paraventricular nucleus placebo group post pregnancy pregnant prevent pup social suckling supraoptic nucleus

项目摘要

1 ABSTRACT 2 Cardiovascular diseases (CVD) are the leading cause of death in women in the US. Women differ from men in 3 rates and timing of CVD and show a stronger association between CVD and metabolic syndrome. This 4 difference suggests that gender-specific factors may moderate the underlying pathophysiology of CVD. We 5 propose that lactation could be one such women-specific factor. Multiple observational studies have linked 6 breastfeeding with reduced maternal cardiometabolic disease later in life; however, the underlying mechanisms 7 for the beneficial effect of lactation remain unknown. Our central hypothesis is that high levels of oxytocin 8 produced during lactation protect breastfeeding mothers against cardiovascular diseases later in life. 9 We were the first to report significantly lower systolic and diastolic blood pressure; less adipose tissue; better 10 cardiac ejection fraction, output, and diastolic function; and lower concentrations of circulating cardiovascular 11 risk markers in mice that lactated compared to mice that did not lactate. Oxytocin (OXT) is a neuropeptide that 12 triggers uterine contractions, the milk let-down reflex during lactation, and plays a central role in maternal 13 behavior and social affiliation. OXT in physiological situations, such as pregnancy and lactation, induces its 14 own synthesis and release. In our model, we found significantly increased circulating OXT levels and mRNA 15 expression in mice that lactated. The objective of this study is to further define the mechanisms affecting 16 maternal cardiovascular and metabolic outcomes after lactation-induced OXT production. We will test 3 17 hypotheses: 1) OXT-stimulating events during lactation – suckling and maternal-pup interaction – are required 18 for dams to develop maternal cardioprotective phenotype later in life; 2) that higher levels of OXT in 19 postpartum lactated mice is a result from activation of central OXT-OXTR system; 3) administration of 20 exogenous OXT to nonlactating mice in the immediate post-delivery period will rescue the cardioprotective 21 phenotype with or without pre-existing chronic disease. Aim 1 is designed to mimic the bottle-feeding situation 22 in non-breastfeeding women; we will use mice with their nipples surgically removed. In Aim 2 we will use 23 conditional knockout mice (flox-Cre recombinase system) that are Oxtr deficient in the brain. In Aim 3 the 24 hypothesis will be tested in obesity-hypertension model. Longitudinal in vivo experimental procedures will 25 include measuring fasting glucose and blood pressure, and assessing cardiac function with echocardiogram 26 and adipose tissue using micro-computed micrography. In vitro, we will utilize organ explant and vascular 27 reactivity studies. In summary, our proposal will define the mechanisms by which lactation affects maternal 28 health later in life and quantify the causal effect of breastfeeding on maternal cardiovascular and metabolic 29 health. The results of our study may lead to further mechanistic explorations of the role of lactation in maternal 30 health, which could be directly translated into interventions to prevent CVD in women.

1摘要 2个心血管疾病（CVD）是美国女性的主要死亡原因。 3 CVD的速率和时机显示了CVD和代谢综合征之间的更强关联 4差异表明，性别特异性因素可能会适应CVD的潜在病理生理 5提出泌乳可能是一个特定于女性的因素。 6母乳喂养以后生命后期减少母体心脏代谢疾病； 7对于泌乳的有益作用，仍然未知。哺乳期间产生的8个保护母亲免受心血管扫描寿命。 9我们报告的收缩压和舒张压明显降低。 10个心脏射血分数，输出和舒张功能；与未乳酸的小鼠相比，小鼠的11个风险标记是一种神经肽。 12个触发子宫收缩，哺乳期间牛奶放松反射，并在母体中起着核心作用 13个行为和社会隶属关系。 14自己的合成和释放。 15乳的表达是进一步定义感情的机制 16母体心血管和代谢结局，哺乳引起的oxt产生。 17个假设：1）在哺乳期和孕妇相互作用期间，牛的刺激事件 - 需要 18大坝以后生命的母体心脏保护表型； 2） 19产后哺乳后的小鼠是中央OXT-OXTR系统的激活的结果； 20在送货后期的外源性牛至非乳酸小鼠将挽救心脏保护 21具有或没有预先疾病的表型。 22在非胸腔喂养的女性中； 23条条件敲除小鼠（Flox-Cre重组酶系统）是大脑中的oxtr缺陷。 24假设将在肥胖 - 亚型模型中进行测试。 25包括测量空腹葡萄糖和血压，以及通过超声心动图评估CardiACC功能 26和脂肪组织使用微型计算机图。 27反应性研究。 28生活中的健康状况，并量化母乳喂养对母亲心血管和代谢的因果关系 29健康的结果。 30健康，可以直接翻译干预措施，以防止女性CVD。