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

项目摘要/摘要 健康饮食可降低心血管疾病(CVD)的风险。植物性饮食，包括 主要是植物食品，动物产品含量较低，这与健康的饮食模式 患心血管疾病的风险较低。然而，植物性饮食与心血管疾病之间联系的确切机制是 人们对此知之甚少。本提案旨在阐明植物性饮食的机制。 利用蛋白质组学和表观遗传学与心血管疾病有关。 本提案的具体目的是：1)确定4个植物性饮食指数的蛋白质特征 [总体植物性饮食指数(PDI)、非素食主义饮食、健康植物性饮食指数(HPDI)和不健康 植物性饮食指数(UPDI)]，2)评估植物性饮食与 蛋白质和事件心血管疾病，以及3)探索4个植物性饮食指数的DNA甲基化特征。这个 建议的研究将使用社区动脉粥样硬化风险(ARIC)研究，这是一项表型丰富的研究 中年非裔美国人和欧洲裔美国人的社区前瞻性研究 膳食摄入量、蛋白质组学和DNA甲基化数据，以及作为发现数据的心血管疾病结果判定 准备好了。弗雷明翰心脏研究和动脉粥样硬化的多种族研究，具有良好的前瞻性 具有类似数据的队列将用于外部验证。目标的完成将识别新的蛋白质， 表观遗传标记，以及可通过植物性饮食改变的途径。这种新奇的证据将是 开发用于早期发现和识别心血管疾病治疗靶点的生物标志物的第一步。 金贤珠博士寻求K01指导研究科学家发展奖以获得Essential 技能、知识和有指导的研究经验，为未来的独立职业生涯做准备 在营养学、多组学和心血管疾病方面具有专业知识的研究员。金博士在研究方面有着良好的记录 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 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。 这项研究提案详细说明了一个五年计划，包括教学课程、动手研究培训、 在Casey Rebholz博士(营养学专家)的主要指导下的职业充实计划 蛋白质组学)，并由Josef Coresh博士(蛋白质组学和血管疾病专家)共同指导， 丹·阿金博士(表观遗传学专家)。卓越的指导团队，除了外部 拥有多学科专业知识的协作者和顾问，以及Johns的高度协作环境 霍普金斯大学彭博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.