Nonalcoholic fatty liver disease, associated lipidomic changes, and preeclampsia risk

非酒精性脂肪肝、相关脂质组学变化和先兆子痫风险

• 批准号: 10591257
• 负责人: Tatyana Kushner
• 金额: $ 19.07万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10591257
• 关键词: Active Learning; Affect; Biological Markers; Biometry; Black race; Blood Vessels; Body mass index; Cardiovascular Diseases; Cardiovascular system; Caring; Clinical; Clinical Investigator; Data; Development; Development Plans; Diabetes Mellitus; Discipline of obstetrics; Eicosanoids; Endothelial Cells; Environment; Enzymes; Epidemiology; Ethnic Origin; Ethnic Population; Functional disorder; Funding; Future; Gestational Diabetes; Goals; Health; Health system; Hepatic; Hepatology; High Prevalence; Hispanic; Hypertension; Impairment; Incidence; Infant; Inflammation; Infrastructure; Institution; Intervention; Knowledge; Lipids; Liver; Liver diseases; Longitudinal cohort; Maternal Health; Maternal Mortality; Measures; Medicaid; Mentorship; Metabolic; Metabolic syndrome; Minority Women; Obesity; Outcome; Overweight; Pathogenesis; Patients; Physicians; Polyunsaturated Fatty Acids; Population; Positioning Attribute; Postpartum Period; Postpartum Women; Pre-Eclampsia; Pregnancy; Pregnant Women; Premature Birth; Prospective Studies; Prospective cohort; Recording of previous events; Regulation; Research; Research Design; Research Personnel; Retrospective Studies; Risk; Risk Factors; Risk Reduction; Role; Syndrome; System; Testing; Training; Translational Research; Underserved Population; United States; Vascular Cell Adhesion Molecule-1; Woman; advanced maternal age; adverse pregnancy outcome; aged; biobank; cardiovascular disorder risk; career development; endothelial dysfunction; epidemiology study; ethnic minority population; high risk; improved; lipid metabolism; lipidomics; liver injury; male; maternal morbidity; maternal outcome; multi-ethnic; newborn adiposity; non-alcoholic fatty liver disease; patient oriented; patient population; pregnancy disorder; prepregnancy; prevent; prospective; racial minority population; reproductive; research and development; sex; systemic inflammatory response

PROJECT SUMMARY Preeclampsia (PE) is a leading cause of maternal morbidity and mortality in the United States which has led to an urgent need to accurately predict its risk. It is not known how nonalcoholic fatty liver disease (NAFLD), the liver manifestation of metabolic syndrome and the most prevalent liver disease among women, contributes to PE risk. The long-term objective of this proposal is to define the relationship between NAFLD and PE, to identify strategies to reduce the risk of PE, and to improve short- and long-term maternal outcomes in this population. This project will evaluate the independent association of NAFLD with PE among overweight and obese women. It will also study relevant lipid alterations in women with NAFLD in pregnancy which are associated with endothelial dysfunction that leads to the clinical syndrome of PE, among NAFLD (compared to non-NAFLD) patients during pregnancy. The Specific Aims of this proposal are: (1) To prospectively assess whether NAFLD is an independent risk factor for: i) PE among overweight/obese women and ii) PE with liver injury; (2) To determine whether women with NAFLD in pregnancy have altered levels of bioactive lipids associated with endothelial cell dysfunction, compared with women without NAFLD in pregnancy. This study will be performed in the Mount Sinai Health System, which provides care to a diverse and multiethnic patient population disproportionately affected by both NAFLD and PE. This application will support the candidate's career development into an independent patient-oriented investigator focused on the influence of liver disease in pregnancy on preeclampsia risk and future maternal cardiovascular and liver health, a significant unmet need. The proposed career development plan integrates advanced coursework in translational epidemiology, lipidomics assessment, prospective study design/ analysis, and biostatistics, and experiential learning through the conduct of the proposed research plan, all within a highly supportive research environment. The mentorship team which includes senior investigators with expertise in epidemiologic and translational research in hepatology (Friedman and Terrault), preeclampsia (Roberts), and prospective study design and advanced biostatistical analysis (Sigel), will guide the candidate's research and career development. The superb institutional infrastructure for developing successful clinical investigators and the substantial institutional commitment to the candidate greatly strengthen this application. At the conclusion of this proposal's funding period, Dr. Kushner will be optimally positioned as an independent physician-investigator studying the intersection of liver disease and PE, and their implications on future maternal health.

项目摘要 先兆子痫（PE）是美国孕产妇发病率和死亡率的主要原因，这导致了 迫切需要准确预测其风险。目前尚不清楚非酒精性脂肪肝（NAFLD）， 代谢综合征的肝脏表现和女性中最常见的肝脏疾病， PE风险。该提案的长期目标是确定NAFLD和PE之间的关系， 确定降低PE风险的策略，并改善这方面的短期和长期孕产妇结局。 人口该项目将评估超重和肥胖人群中NAFLD与PE的独立关联， 肥胖的女人它还将研究妊娠期NAFLD女性的相关脂质变化， 与导致PE临床综合征的内皮功能障碍相关，在NAFLD中（与 非NAFLD）患者。本建议的具体目的是：（1）前瞻性评估 NAFLD是否是以下疾病的独立风险因素：i）超重/肥胖女性中的PE和ii）肝脏PE （2）确定妊娠期NAFLD女性是否具有生物活性脂质水平的改变 与妊娠期无NAFLD的女性相比，与内皮细胞功能障碍相关。本研究 将在西奈山卫生系统进行，该系统为多样化和多种族的患者提供护理 受NAFLD和PE影响的人群不成比例。此应用程序将支持候选人的 职业发展成为一名独立的以患者为导向的研究者，专注于肝病的影响 在妊娠期先兆子痫风险和未来产妇心血管和肝脏健康方面， 需要的拟议的职业发展计划整合了转化流行病学的高级课程， 脂质组学评估，前瞻性研究设计/分析，生物统计学，以及通过 在一个高度支持的研究环境中进行拟议的研究计划。的 导师团队，包括具有流行病学和转化研究专业知识的高级研究人员 在肝病学（Friedman和Terrault），先兆子痫（Roberts），前瞻性研究设计和先进的 生物统计分析（西格尔），将指导候选人的研究和职业发展。的高超 培养成功的临床研究者的制度基础设施和实质性的制度基础设施 对候选人的承诺大大加强了这一应用。在这项提案的资金结束时， 在此期间，库什纳博士将被最佳定位为一名独立的医生-研究者， 肝病和PE的交叉点及其对未来孕产妇健康的影响。