Lactation Effects on Postnatal Endothelial Function and Vascular Inflammation

描述（由申请人提供）：与纯母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）的风险增加。这种关联背后的机制仍有待确定。本研究的长期目标是确定哺乳降低心血管风险的生物学机制，从而揭示早期干预的目标。本应用程序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动脉粥样硬化和高血压疾病发病的早期原因。从怀孕到产后早期的过渡以内皮损伤的显著增加为特征，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，产后可能是血管内皮炎症损伤风险增加的关键时期。中心假设是，在产后关键的第一年，哺乳通过对内皮功能的有益作用降低心血管风险。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。提出这项研究的基本原理是，通过确定哺乳减少内皮功能障碍的机制，将确定降低产妇心血管疾病风险的新治疗靶点。这一假设将通过三个特定目标进行验证：1)确定哺乳对内皮功能的影响，以产后2、6和12个月的肱动脉血流介导扩张（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)测量泌乳对内皮功能受损代谢危险因素的影响。这些目标将通过在妊娠晚期招募120名初产妇的纵向研究来实现，并对低社会经济地位、超重和非裔美国妇女进行过采样，这些妇女未来患心血管疾病的风险增加。在妊娠晚期评估婴儿喂养意向。促炎和代谢生物标志物将在妊娠晚期、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在产后2个月婴儿喂养前后通过FMD评估。第一年的FMD %变化将用于测试饲养方法和泌乳特征（持续时间、强度、泌乳激素）对内皮功能的累积影响。这种方法是创新的，因为迄今为止还没有研究在产后第一年检查泌乳对内皮功能、炎症和代谢的影响，而这一时期血管内皮最容易受到损伤，并且可以观察到泌乳的急性效应。拟议的研究意义重大，因为它有望促进对心血管疾病（美国女性死亡的头号原因）早期机制的理解，并有可能对女性健康产生广泛的积极影响。

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.