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

基本信息

批准号：
8850897
负责人：
Karen M Grewen
金额：
$ 46.28万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-09 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8850897
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 Future Glucocorticoids Glucose Goals Health 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&apos s Health adrenergic base brachial artery cardiovascular disorder risk cardiovascular risk factor clinical practice critical period cytokine disorder risk endothelial dysfunction feeding improved indexing inflammatory marker injured innovation killings new therapeutic target postnatal receptor response vascular endothelial dysfunction vascular inflammation waist circumference

项目摘要

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）：与练习独家或长期泌乳的母亲相比，不母乳喂养婴儿的母亲和早期断奶的母亲患心血管疾病（CVD）的风险增加。该关联的基础机制仍有待确定。这项研究的长期目标是确定泌乳降低心血管风险的生物学机制，从而揭示了早期干预的靶标。该应用的目的是确定泌乳对血管内皮功能障碍的影响，这是动脉粥样硬化和高血压疾病发病机理的早期因果因素。从妊娠到产后早期的过渡的特征是对内皮损害的有效贡献明显增加，包括增加的系统性和局部炎症介质，循环脂质和内脏脂肪。因此，产后时期像围绝经期一样，可能是增加对血管内皮炎症损害风险的关键时期。中心假设是，泌乳通过对产后批评者对内皮功能的有益影响来降低心血管风险。该假设基于申请人实验室中收集的初步数据，并得到了已发表的文献的支持。拟议的研究的理由是，确定泌乳减少内皮功能障碍的机制将确定降低Parous妇女CVD风险的新治疗靶标。该假设将使用三个特定目的进行检验：1）确定泌乳对内皮功能的影响，并通过在产后2、6和12个月评估的臂动脉流介导的扩张（FMD）索引； 2）量化泌乳对有助于内皮功能障碍的全身性和血管炎症介质的影响； 3）测量泌乳对损害内皮功能的代谢危险因素的影响。这些目标将通过对怀孕三个月招募的120名初学妇女的纵向研究来实现，并对低SES，超重和非裔美国妇女进行过多采样，这些妇女对未来CVD的风险增加了。婴儿喂养意愿将在三个月评估。促炎和代谢生物标志物将在三个月以及产后2、6和12个月进行评估。乳房或奶瓶喂养的急性内皮作用将通过在产后2个月前后喂养前后评估的FMD来测量。第一年的FMD％变化将用于测试进食方法和泌乳特征（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，因为迄今为止尚无研究检查泌乳对内皮功能，炎症和代谢的影响，当时第一年，当血管内皮可能最容易受到损伤时，并且可能观察到泌乳的急性影响。拟议的研究之所以重要，是因为有望提高对CVD早期机制的理解，CVD是美国妇女的死亡原因，并具有对妇女健康的广泛积极影响的潜力。