Stress, inflammation and coronary endothelial injury in preeclampsia

妊娠期高血压疾病，如先兆子痫（PEC），会引起显著的孕产妇死亡。 发病率和死亡率，并已成为一个重要的早期生命，并可能改变，风险因素 年轻女性心脏病的发病率。PEC在妊娠20周后被诊断为新发高血压 有终末器官损伤的证据，认为是由于胎盘缺血和 血管生成重要的是，PEC与CVD风险显著增加相关， 生命，远远超过怀孕期。了解PEC如何影响心血管（CV）健康， 生物和社会行为的角度（即，社会建构的性别角色和压力）对于 告知风险沟通、分层，并确定和瞄准新的治疗方法，以减少CV疾病 (CVD)尤其是年轻、高风险的女性。 尽管PEC患者通常具有传统的孕前CV风险因素，如2型 糖尿病和肥胖，这些风险因素不能完全解释妊娠后CV风险的升高 PEC的复杂性。认为导致PEC发病和损伤内皮细胞的两个因素 细胞是血管生成的不平衡和肾素-血管紧张素系统（RAS）的改变，由 胎盘缺血并导致氧化应激和全身炎症。从一个社会行为 有证据表明，健康和心理压力的社会决定因素影响PEC 严重程度和未来CVD结果。女性的生活经验，包括她们的社会经验 建构的性别角色、压力和邻里因素对PEC的健康结果有显著影响。我们 最近开发的无创、可重复的基于MRI的方法来测量冠状动脉内皮功能 (CEF)，提供了一种手段来探测机制有助于冠状动脉疾病（CAD）的病理生理学 产后妇女与最近PEC。异常CEF在肿瘤的发生、发展、转归中起着重要作用 和CAD的临床表现，独立预测CV事件，并且是医学治疗的目标。 干预措施。在本申请中，我们提出在患有PEC的产后妇女中确定：1）CEF， 和炎症/不平衡的血管生成的标志物是负相关的，和2）是否测量 压力（心理社会压力和生理测量）与内皮异常相关 产后高血压我们将确定，在有PEC病史的妇女中，减少CEF是否可以 至少部分地可以通过增加的炎症/异常血管生成/应激来解释。综合这些 研究将为PEC女性CVD风险增加提供新的病理生理学见解， 这些因素是导致血管功能障碍的主要原因。这项研究，如果资助，将解决重要的知识， 关于影响年轻人产后血管健康的性别和性别特异性变量的差距 并为设计未来的干预研究提供数据，以改善PEC的健康结局。

Hypertensive disorders of pregnancy, such as preeclampsia (PEC) cause significant maternal morbidity and mortality, and have emerged as an important early life, and potentially modifiable, risk factor of heart disease in younger women. PEC is diagnosed as new onset hypertension after 20 weeks gestation with evidence of end organ damage, thought to occur because of placental ischemia and an imbalance of angiogenesis. Importantly, PEC is associated with significantly increased CVD risk that persists into later life, far beyond the pregnancy period. Understanding how PEC affects cardiovascular (CV) health both from a biological and socio-behavioral perspective (ie. socially constructed gender roles and stress) is critical to inform risk communication, stratification and to identify and target new treatments to reduce CV disease (CVD), especially among young, high risk women. Although patients with PEC often have traditional pre-pregnancy CV risk factors such as type 2 diabetes and obesity, these risk factors do not fully explain the elevated CV risk conferred after a pregnancy complicated by PEC. Two factors thought to contribute to the pathogenesis of PEC and injure endothelial cells are an imbalance of angiogenesis and alterations in renin-angiotensin-system (RAS), driven by placental ischemia and resulting in oxidative stress with systemic inflammation. From a socio-behavioral perspective, there is evidence that social determinants of health and psychological stress influence PEC severity and future CVD outcomes. Women’s lived experience, including how they experience socially constructed gender roles, stress and neighborhood factors affect health outcomes significantly in PEC. We recently developed noninvasive, reproducible MRI-based methods to measure coronary endothelial function (CEF), offering a means to probe mechanisms contributing to coronary artery disease (CAD) pathophysiology in postpartum women with recent PEC. Abnormal CEF plays a critical role in the development, progression and clinical manifestations of CAD, independently predicts CV events, and is a target for medical interventions. We propose in this application to determine in postpartum women with PEC: 1) whether CEF, and markers of inflammation/imbalanced angiogenesis are inversely related and 2) whether measures of stress (both psychosocial stress and physiologic measures) are associated with endothelial abnormalities and postpartum hypertension. We will determine, in women with a history of PEC, whether reduced CEF can be explained, at least in part, by increased inflammation/abnormal angiogenesis/stress. Together these studies will offer new pathophysiologic insights into increased CVD risk in women with PEC, and which factors contribute most to vascular dysfunction. This study, if funded, will address significant knowledge gaps regarding sex and gender specific variables that affect postpartum vascular health in young women and provide data to design future interventional studies to improve health outcomes in PEC.