Proteomic and epigenetic alterations associated with plant-based diets and CVD

与植物性饮食和心血管疾病相关的蛋白质组学和表观遗传改变

• 批准号: 10900009
• 负责人: Hyunju Kim
• 金额: $ 9.25万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-02 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10900009
• 关键词: Adherence; Affect; African American; American; Animals; Area; Atherosclerosis Risk in Communities; Biological; Biological Process; Biology; Blood Pressure; Body mass index; Cardiovascular Diseases; Cardiovascular system; Communities; DNA Methylation; Data; Data Discovery; Data Set; Diet; Dietary Practices; Dietary intake; Dimensions; Disease Outcome; Doctor of Philosophy; Early identification; Eating; Edible Plants; Elasticity; Ensure; Epidemiology; Epigenetic Process; Etiology; European; Event; Five-Year Plans; Food; Framingham Heart Study; Future; Gene Expression; Genes; Goals; Homeostasis; Inflammation; Inflammatory; Knowledge; Link; Machine Learning; Mentored Research Scientist Development Award; Mentors; Mentorship; Metabolic; Metabolism; Methylation; Methyltransferase; Multi-Ethnic Study of Atherosclerosis; Multiomic Data; Nutritional; Nutritional Study; Pathogenesis; Pathway interactions; Pattern; Phenotype; Plants; Prevention strategy; Production; Productivity; Prospective Studies; Prospective cohort; Proteins; Proteome; Proteomics; Public Health Schools; Publishing; Recommendation; Research; Research Personnel; Research Proposals; Research Training; Risk Factors; Risk Reduction; Sample Size; Statistical Models; Techniques; Technology; Training; Validation; Vascular Diseases; Vegan Diet; adjudication; aptamer; cardiometabolic risk; cardioprotection; cardiovascular disorder prevention; cardiovascular disorder risk; career; cohort; collaborative environment; dietary guidelines; early detection biomarkers; epigenetic marker; experience; follow-up; good diet; hands on research; indexing; metabolome; metabolomics; methylation pattern; methylome; middle age; multidisciplinary; multiple omics; novel; nutrition; nutritional epidemiology; prevent; programs; prospective; protein biomarkers; skills; therapeutic target; treatment strategy

Project Summary / Abstract Healthy diets reduce the risk of cardiovascular disease (CVD). Plant-based diets, which are comprised predominantly of plant foods and are low in animal products, are healthy dietary patterns that are associated with a lower risk of CVD. However, the precise mechanisms underlying plant-based diet-CVD associations are poorly understood. The present proposal aims to elucidate the mechanisms through which plant-based diets are associated with CVD using proteomics and epigenetics. Specific aims of the present proposal are to: 1) identify protein signatures of 4 plant-based diet indices [overall plant-based diet index (PDI), provegetarian diet, healthy plant-based diet index (hPDI), and unhealthy plant-based diet index (uPDI)], 2) evaluate the prospective associations between plant-based diet-related proteins and incident CVD, and 3) explore DNA methylation signatures of 4 plant-based diet indices. The proposed study will use the Atherosclerosis Risk in Communities (ARIC) study, a richly phenotyped community-based prospective study of middle-aged African American and European American with usual dietary intake, proteomics and DNA methylation data, and adjudicated CVD outcomes as the discovery data set. Framingham Heart Study and Multi-Ethnic Study of Atherosclerosis, well-characterized prospective cohorts with similar data, will be used for external validation. Completion of the aims will identify novel proteins, epigenetic markers, and pathways that are modifiable by plant-based diets. Such novel evidence will be the first step for developing biomarkers for early detection and identifying therapeutic targets of CVD. Hyunju Kim, PhD seeks a K01 Mentored Research Scientist Development Award to acquire essential skills, knowledge, and mentored research experience to prepare for a future career as an independent investigator with expertise in nutrition, multi-omics, and CVD. Dr. Kim has a track record of research productivity in the areas of nutritional epidemiology and nutritional metabolomics. However, Dr. Kim needs additional training in proteomics, epigenetics, and cardiovascular biology to achieve research independence. This research proposal details a five-year plan consisting of didactic coursework, hands-on research training, career enrichment programs under the primary mentorship of Dr. Casey Rebholz, PhD (expert in nutritional proteomics), and co-mentorship by Dr. Josef Coresh, MD, PhD (expert in proteomics and vascular disease), and Dr. Dan Arking, PhD (expert in epigenetics). The exceptional mentoring team in addition to external collaborators and advisors with multi-disciplinary expertise, and a highly collaborative environment at Johns Hopkins Bloomberg School of Public Health will ensure the successful transition of Dr. Kim into an independent investigator.

项目摘要 /摘要 健康饮食降低了心血管疾病（CVD）的风险。植物性饮食，包括 主要是植物食品，动物产品低，是健康的饮食模式 CVD风险较低。但是，基于植物的饮食-CVD关联的确切机制是 理解不佳。本提案旨在阐明基于植物的饮食的机制 使用蛋白质组学和表观遗传学与CVD相关。 本提案的具体目的是：1）确定4个基于植物的饮食指数的蛋白质特征 [总体植物性饮食指数（PDI），证明饮食，健康植物性饮食指数（HPDI）和不健康 基于植物的饮食指数（UPDI）]，2）评估基于植物饮食相关的植物饮食之间的前瞻性关联 蛋白质和入射CVD以及3）探索4个基于植物的饮食指数的DNA甲基化特征。这 拟议的研究将在社区（ARIC）研究中使用动脉粥样硬化风险，这是一项丰富的表型 基于社区的中年非裔美国人和欧洲美国人的前瞻性研究 作为发现数据的饮食摄入，蛋白质组学和DNA甲基化数据以及裁定的CVD结果 放。 Framingham心脏研究和动脉粥样硬化的多种族研究 具有类似数据的同类人群将用于外部验证。目的的完成将确定新型蛋白质， 表观遗传标记和通过基于植物的饮食进行修改的途径。这种新颖的证据将是 开发生物标志物以早期检测和识别CVD治疗靶标的第一步。 Hyunju Kim，博士寻求K01指导的研究科学家发展奖，以获得必需品 技能，知识和指导的研究经验，为作为独立的未来职业做准备 研究人员具有营养，多词和CVD方面的专业知识。金博士有研究的记录 营养流行病学和营养代谢组学领域的生产力。但是，金博士需要 蛋白质组学，表观遗传学和心血管生物学的其他培训，以实现研究独立性。 该研究建议详细介绍了一个五年计划，包括教学课程，动手研究培训， Casey Rebholz博士的主要指导下的职业丰富计划（营养专家 蛋白质组学）和博士Josef Coresh博士（蛋白质组学和血管疾病专家）和授权 以及博士（表观遗传学专家）Dan Arking博士。除外部外，杰出的指导团队 与多学科专业知识的合作者和顾问，以及约翰斯的高度协作环境 霍普金斯彭博公共卫生学院将确保金博士成功过渡到独立 研究者。