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

项目概要/摘要 健康的饮食可以降低心血管疾病（CVD）的风险。植物性饮食， 主要是植物性食物，动物产品含量低，是健康的饮食模式， 患心血管疾病的风险更低。然而，植物性饮食与心血管疾病相关的确切机制是 不太了解。本提案旨在阐明植物性饮食的机制， 与心血管疾病有关。 本提案的具体目标是：1）确定4种植物性饮食指数的蛋白质特征 [总体植物性饮食指数（PDI），亲素食饮食，健康植物性饮食指数（hPDI），不健康饮食指数（hPDI）] 植物性饮食指数（uPDI）]，2）评估植物性饮食相关的 蛋白质和事件CVD，和3）探索4植物性饮食指数的DNA甲基化特征。的 拟议的研究将使用社区动脉粥样硬化风险（ARIC）研究，一个丰富的表型 一项针对中年非裔美国人和欧美人的基于社区的前瞻性研究， 饮食摄入、蛋白质组学和DNA甲基化数据，以及裁定的CVD结果作为发现数据 集心功能不全研究和多种族动脉粥样硬化研究，充分表征的前瞻性 具有类似数据的队列将用于外部验证。目标的完成将识别出新型蛋白质， 表观遗传标记，以及植物性饮食可改变的途径。这种新的证据将是 这是开发用于早期检测和鉴定CVD治疗靶点的生物标志物的第一步。 Hyunju Kim博士寻求K 01指导研究科学家发展奖，以获得必要的 技能，知识和指导的研究经验，为未来的职业生涯作为一个独立的准备 在营养学、多组学和心血管疾病方面具有专长的研究者。金博士有一个研究记录 在营养流行病学和营养代谢组学领域的生产力。然而，金博士需要 在蛋白质组学，表观遗传学和心血管生物学方面的额外培训，以实现研究独立性。 该研究提案详细介绍了一个五年计划，包括教学课程、实践研究培训， 在凯西雷布霍尔茨博士（营养学专家）的主要指导下， 蛋白质组学），并由Josef Coresh博士，医学博士，博士（蛋白质组学和血管疾病专家）共同指导， 和丹·阿金博士（表观遗传学专家）。除了外部的优秀指导团队， 具有多学科专业知识的合作者和顾问，以及Johns的高度协作环境 霍普金斯布隆伯格公共卫生学院将确保金博士成功过渡到独立的 调查员

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.