Lactation Effects on Postnatal Endothelial Function and Vascular Inflammation

描述（由申请人提供）：与实行纯母乳喂养或延长哺乳期的母亲相比，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。这种联系的内在机制仍有待确定。这项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。从妊娠到产后早期的过渡期的特征是内皮损伤的潜在贡献者显著增加，包括全身和局部炎症介质、循环脂质和内脏脂肪增加。因此，产后期与围绝经期一样，可能是血管内皮炎性损伤风险增加的关键时期。中心假设是哺乳通过其对产后关键第一年内皮功能的有益影响降低心血管风险。该假设基于申请人实验室收集的初步数据，并得到了已发表文献的进一步支持。提出这项研究的理由是，确定哺乳减少内皮功能障碍的机制将确定新的治疗靶点，以减少经产妇女的心血管疾病风险。将使用三个具体目标来检验该假设：1）确定哺乳对内皮功能的影响，通过在产后2、6和12个月评估的肱动脉血流介导的扩张（FMD）来索引; 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）测量哺乳对损害内皮功能的代谢危险因素的影响。这些目标将通过一项纵向研究来实现，该研究招募了120名在妊娠晚期分娩的妇女，对低SES、超重和非洲裔美国妇女进行过采样，这些妇女未来CVD的风险增加。婴儿喂养意愿将在第三个三个月进行评估。促炎和代谢生物标志物将在孕晚期以及产后2、6和12个月进行评估。母乳喂养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来测量。第一年期间的FMD %变化将用于检测喂养方法和泌乳特征（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检查哺乳对内皮功能，炎症和代谢的影响，在产后的第一年，当血管内皮可能是最容易受到伤害，当哺乳的急性影响可能会被观察到。这项研究意义重大，因为它有望促进对CVD早期机制的理解，CVD是美国女性死亡的头号原因，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.