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.

项目总结 先兆子痫(PE)是美国孕产妇发病率和死亡率的主要原因，已导致 迫切需要准确预测其风险。目前尚不清楚非酒精性脂肪性肝病(NAFLD)是如何 代谢综合征的肝脏表现和女性中最常见的肝病，有助于 PE风险。这项建议的长期目标是界定NAFLD和PE之间的关系，以 确定降低PE风险的策略，并在这方面改善孕产妇的短期和长期结局 人口。本项目将评估NAFLD与PE在超重和肥胖人群中的独立相关性 肥胖的女人。它还将研究妊娠期间患有NAFLD的妇女的相关血脂变化。 在NAFLD中，与导致PE临床综合征的内皮功能障碍有关(与 非非酒精性脂肪肝)患者在怀孕期间。这项建议的具体目标是：(1)前瞻性评估 非酒精性脂肪肝是否为：i)超重/肥胖女性发生PE和ii)合并肝脏PE的独立危险因素 损伤；(2)确定妊娠期非酒精性脂肪肝患者是否改变了生物活性脂类水平 与妊娠期无NAFLD的妇女相比，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，该系统为不同种族和多民族的患者提供护理 NAFLD和PE对人群的影响不成比例。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人员，专注于肝病的影响 妊娠期对子痫前期风险和未来母亲心血管和肝脏健康的影响 需要。拟议的职业发展计划整合了翻译流行病学的高级课程， 脂质组学评估、前瞻性研究设计/分析、生物统计学和经验性学习 拟议研究计划的实施，所有这些都是在高度支持的研究环境中进行的。这个 导师团队，包括在流行病学和翻译研究方面具有专业知识的高级调查人员 肝病学(Friedman和Terrault)、子痫前期(Roberts)和前瞻性研究设计和高级 生物统计分析(SIGEL)，将指导应聘者的研究和职业发展。一流的 培养成功的临床研究人员的机构基础设施和实质性的机构 对候选人的承诺极大地加强了这一申请。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研究 肝病和PE的交叉及其对未来孕产妇健康的影响。