Lactation Effects on Postnatal Endothelial Function and Vascular Inflammation

哺乳期对产后内皮功能和血管炎症的影响

• 批准号: 8439437
• 负责人: Karen M Grewen
• 金额: $ 43.74万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-09 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8439437
• 关键词: Acute; Adrenergic Agents; African American; Anti-Inflammatory Agents; Anti-inflammatory; Binding; Biological; Biological Markers; Blood Vessels; Body Weight decreased; Bottle feeding; Breast Feeding; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cell Adhesion Molecules; Cells; Characteristics; Chronic Disease; Coupled; Data; Dose; Early Intervention; Endothelin-1; Endothelium; Estrogens; Event; Fasting; Fatty acid glycerol esters; Feeding Methods; Female; Functional disorder; Future; Glucocorticoids; Glucose; Goals; High Density Lipoproteins; Hormonal; Hormones; Hydrocortisone; Hyperlipidemia; Hypertension; Hypertriglyceridemia; Immune; Infant; Inflammation; Inflammation Mediators; Inflammatory; Injury; Insulin; Insulin Resistance; Intention; Interleukin-1; Interleukin-10; Interleukin-4; Interleukin-6; Laboratories; Lactates; Lactation; Lipids; Literature; Longitudinal Studies; Low-Density Lipoproteins; Measures; Mediating; Metabolic; Metabolism; Mission; Mothers; Nitric Oxide; Obesity; Overweight; Oxytocin; Pathogenesis; Perimenopause; Perinatal; Plasma; Population; Postpartum Period; Pregnancy; Production; Prolonged Lactations; Public Health; Publishing; Recruitment Activity; Research; Risk; Risk Factors; Sum; Surface; TNF gene; Testing; Third Pregnancy Trimester; Time; Translating; Vascular Endothelium; Vasoconstrictor Agents; Vasodilation; Visceral; Weaning; Woman; Women' s Health; adrenergic; base; brachial artery; cardiovascular disorder risk; cardiovascular risk factor; clinical practice; critical period; cytokine; disorder risk; feeding; improved; indexing; inflammatory marker; injured; innovation; killings; new therapeutic target; postnatal; public health relevance; receptor; response; vascular endothelial dysfunction; vascular inflammation; waist circumference

DESCRIPTION (provided by applicant): Mothers who do not breastfeed their infants and those who wean early are at increased risk of cardiovascular disease (CVD) compared with mothers who practice exclusive or prolonged lactation. Mechanisms underlying this association remain to be determined. The long-term goal of this research is to identify biological mechanisms through which lactation reduces cardiovascular risk, thereby revealing targets for early intervention. The objective of this application is to determine the effect of lactation on vascular endothelial dysfunction, which is an early causal factor in the pathogenesis of atherogenic and hypertensive disease. The transition from pregnancy to early postpartum is characterized by marked increase in potent contributors to endothelial damage, including increased systemic and local inflammatory mediators, circulating lipids and visceral fat. The postpartum period, like the perimenopause, may therefore be a critical period of enhanced risk for inflammatory damage to vascular endothelium. The central hypothesis is that lactation reduces cardiovascular risk through its salutary effects on endothelial function during the critica 1st year postpartum. This hypothesis is based on preliminary data collected in the applicant's laboratory and is further supported by published literature. The rationale for the proposed research is that determining mechanisms through which lactation reduces endothelial dysfunction will identify new therapeutic targets for reduction of CVD risk among parous women. This hypothesis will be tested using three specific aims: 1) Determine the effect of lactation on endothelial function, indexed by brachial artery flow-mediated dilation (FMD) assessed at 2, 6 and 12 months postpartum; 2) Quantify the effect of lactation on systemic and vascular inflammatory mediators that contribute to endothelial dysfunction; 3) Measure the effect of lactation on metabolic risk factors that impair endothelial function. These aims will be achieved through a longitudinal study of 120 primiparous women recruited in the third trimester of pregnancy, with oversampling of low SES, overweight, and African-American women, who are at increased risk for future CVD. Infant feeding intention will be assessed at 3rd trimester. Pro-inflammatory and metabolic biomarkers will be assessed at 3rd trimester, and at 2, 6 and 12 months postpartum. Acute endothelial effects of breast- or bottle-feeding will be measured by FMD assessed before and after infant feeding at 2 months postpartum. FMD % change during the first year will be used to test the cumulative effects of feeding method and lactation characteristics (duration, intensity, lactation hormones) on endothelial function. The approach is innovative because no studies to date have examined effects of lactation on endothelial function, inflammation and metabolism during the first postpartum year, when vascular endothelium may be most susceptible to injury, and when acute effects of lactation may be observed. The proposed research is significant because it is expected to advance understanding of early mechanisms of CVD, the #1 cause of death for women in the U.S, and has potential for widespread positive impact on women's health.

描述（由申请人提供）：与纯哺乳或长时间哺乳的母亲相比，不母乳喂养婴儿和过早断奶的母亲患心血管疾病 (CVD) 的风险更高。这种关联的潜在机制仍有待确定。这项研究的长期目标是确定哺乳期降低心血管风险的生物学机制，从而揭示早期干预的目标。本申请的目的是确定哺乳对血管内皮功能障碍的影响，血管内皮功能障碍是致动脉粥样硬化和高血压疾病发病机制的早期致病因素。从怀孕到产后早期的过渡的特点是内皮损伤的有效因素显着增加，包括全身和局部炎症介质、循环脂质和内脏脂肪的增加。因此，与围绝经期一样，产后期可能是血管内皮炎症损伤风险增加的关键时期。核心假设是，哺乳期通过其在产后第一年的关键时期对内皮功能的有益作用来降低心血管风险。该假设基于申请人实验室收集的初步数据，并得到已发表文献的进一步支持。拟议研究的基本原理是，确定哺乳减少内皮功能障碍的机制将为降低经产妇女的 CVD 风险确定新的治疗目标。这一假设将通过三个具体目标进行检验： 1) 确定哺乳对内皮功能的影响，以产后 2、6 和 12 个月评估的肱动脉血流介导的扩张 (FMD) 为指标； 2) 量化哺乳对导致内皮功能障碍的全身和血管炎症介质的影响； 3) 测量哺乳期对损害内皮功能的代谢危险因素的影响。这些目标将通过对 120 名妊娠晚期初产妇进行纵向研究来实现，其中对低 SES、超重和非裔美国女性进行过采样，这些女性未来罹患 CVD 的风险较高。婴儿喂养意愿将在妊娠第三个月进行评估。促炎和代谢生物标志物将在妊娠第三个月以及产后 2、6 和 12 个月进行评估。母乳或奶瓶喂养的急性内皮效应将通过产后 2 个月婴儿喂养前后评估的 FMD 进行评估。第一年的 FMD 百分比变化将用于测试喂养方法和哺乳特征（持续时间、强度、哺乳激素）对内皮功能的累积影响。该方法具有创新性，因为迄今为止还没有研究检查哺乳对产后第一年内皮功能、炎症和代谢的影响，此时血管内皮可能最容易受到损伤，并且可能观察到哺乳的急性影响。拟议的研究意义重大，因为它有望增进对心血管疾病（美国女性第一大死因）早期机制的了解，并有可能对女性健康产生广泛的积极影响。