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