Stress, inflammation and coronary endothelial injury in preeclampsia

先兆子痫的应激、炎症和冠状动脉内皮损伤

• 批准号: 10531778
• 负责人: Allison G Hays
• 金额: $ 43.21万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-02 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10531778
• 关键词: Address; Affect; Angiotensins; Atherosclerosis; Autoantibodies; Biological; Biological Markers; Biology; Blood Vessels; Cardiology; Cardiovascular Diseases; Cardiovascular system; Centers of Research Excellence; Cessation of life; Clinic; Clinical; Communication; Coronary; Coronary Arteriosclerosis; Data; Depressed mood; Development; Diagnosis; Discipline of obstetrics; Disease; Disease Outcome; Elderly; Endocrinology; Endothelial Cells; Endothelium; Event; Functional disorder; Funding; Future; Gender; Gender Role; General Population; Health; Heart Diseases; Hematological Disease; High Risk Woman; Hormones; Human; Hypertension; Imaging Techniques; Impairment; Inflammation; Injury; Intervention; Intervention Studies; Ischemia; Knowledge; Lead; Life; Link; Magnetic Resonance Imaging; Maternal Mortality; Measures; Medical; Methods; Myocardial Infarction; Neighborhoods; Nodal; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Organ; Outcome; Oxidative Stress; Pathogenesis; Patients; Physiological; Play; Population; Postpartum Hypertension; Postpartum Period; Postpartum Women; Pre-Eclampsia; Pregnancy; Pregnancy Histories; Prognostic Marker; Prospective Studies; Psychological Stress; Psychosocial Stress; Public Health; Receptor, Angiotensin, Type 1; Recording of previous events; Renin-Angiotensin System; Reporting; Reproducibility; Resources; Risk; Risk Factors; Role; Severities; Social Behavior; Specialized Center; Stratification; Stress; Techniques; Testing; Time; United States National Institutes of Health; Vascular Diseases; Woman; Work; age group; angiogenesis; base; blood pressure elevation; cardioprotection; cardiovascular health; cardiovascular risk factor; cohort; design; disorder risk; endothelial dysfunction; experience; heart disease risk; high risk population; imaging biomarker; improved; inflammatory marker; insight; maternal morbidity; modifiable risk; mortality; multidisciplinary; non-invasive imaging; normotensive; novel; novel therapeutic intervention; perceived stress; pregnancy disorder; prepregnancy; prevent; programs; recruit; sex; social; social health determinants; systemic inflammatory response; vascular injury; young woman

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.

妊娠期高血压疾病，如先兆子痫(PEC)，导致显著的母体 发病率和死亡率，并已成为一个重要的早期生命和潜在的可改变的风险因素 年轻女性罹患心脏病的风险。妊娠20周后PEC被诊断为新发高血压 有终末器官损伤的证据，被认为是由于胎盘缺血和 血管生成。重要的是，PEC与显著增加的心血管疾病风险有关，这种风险会持续到后来 生命，远远超过了怀孕期。从以下两方面了解PEC如何影响心血管(CV)健康 生物学和社会行为观点(即社会构建的性别角色和压力)对 告知风险沟通、分层，并确定和瞄准新的治疗方法以减少心血管疾病 (心血管疾病)，特别是年轻的高危妇女。 尽管PEC患者通常有传统的孕前心血管危险因素，如2型 糖尿病和肥胖，这些危险因素不能完全解释怀孕后心血管风险增加的原因。 被PEC复杂化了。两种因素被认为参与了PEC的发病和内皮损伤 细胞是血管生成的失衡和肾素-血管紧张素系统(RAS)的变化，由 胎盘缺血并导致氧化应激和全身炎症。从一种社会行为 有证据表明，健康和心理压力的社会决定因素会影响PEC 严重程度和未来的心血管疾病结局。女性的生活经历，包括她们如何经历社会 被建构的性别角色、压力和邻里因素对PEC的健康结局有显著影响。我们 最近开发的基于MRI的无创、可重复性的方法来测量冠状动脉内皮功能 (CEF)，提供了一种探索导致冠状动脉疾病(CAD)病理生理机制的手段 最近发生PEC的产后妇女。CEF异常在糖尿病的发生、发展中起关键作用 和冠心病的临床表现，独立预测心血管事件，是医学研究的目标 干预措施。我们建议在此应用程序中确定患有PEC的产后妇女：1)CEF， 炎症/血管生成失衡的标记物是负相关的，2)衡量 应激(心理应激和生理应激)与内皮功能异常有关。 和产后高血压。我们将确定，在有PEC病史的女性中，CEF减少是否可以 至少部分原因是炎症/异常血管生成/应激增加。把这些放在一起 研究将对患有PEC的女性心血管风险增加提供新的病理生理学见解， 导致血管功能障碍的因素最多。这项研究，如果得到资助，将涉及重要的知识 影响年轻人产后血管健康的性别和性别特定变量的差异 并提供数据，以设计未来的干预研究，以改善PEC的健康结果。