Discovery, Replication, and Validation of Biomarkers of the DASH Diet and Hypertension

摘要 饮食是对全球公共健康最严重威胁之一的可改变风险因素：心血管疾病 疾病停止高血压的饮食方法（DASH）饮食模式是高血压的一个例子。 高质量的饮食，水果，蔬菜，低脂乳制品和低钠，饱和脂肪， 胆固醇DASH饮食被广泛认为是预防高血压的有效方法， 心血管疾病和相关的心脏代谢疾病。现有的饮食摄入生物标志物很少 代表单一营养素而不是整体饮食模式。代谢组学和蛋白质组学是高- 用于有效测量生物样品中的化合物的通量方法。代谢组 反映所消耗的食物的分解产物，不仅可以代表食物及其 还有饮食模式。蛋白质组代表生物学功能和活性， 补充了代谢组学特征我们建议进行非靶向代谢组学和蛋白质组学， DASH饮食的新生物标志物以及DASH饮食介导的血液的生物标志物的发现 减压研究结果将在两个独立的研究人群中重复，并通过使用 候选生物标志物的靶向定量测定。这一具有成本效益的提议利用了 NHBLI BioLINCC储存库中的研究数据和生物标本以及现有的组学数据。研究 团队由K01资助的早期研究人员领导，他接受过饮食和慢性代谢组学的培训。 疾病结果。研究小组成员是已确定的，有以下病史的高级研究者： 与主要研究者的合作以及营养生物化学方面的互补专业知识， 非靶向代谢组学和蛋白质组学平台、实验室方法学、生物统计学、饮食摄入量、血液 压力，以及对研究人群的深入了解。这项研究将 推进目前评估饮食摄入量的方法，并将为临床重要的饮食提供见解， 改变代谢途径。

ABSTRACT Diet is a modifiable risk factor for one of the most serious threats to global public health: cardiovascular disease. The Dietary Approaches to Stop Hypertension (DASH) dietary pattern is one example of a high- quality diet that is high in fruits, vegetables, and low-fat dairy products and low in sodium, saturated fat, and cholesterol. The DASH diet is widely recognized as an effective approach for the prevention of hypertension, cardiovascular disease, and related cardiometabolic diseases. Existing biomarkers of dietary intake are few and represent single nutrients rather than a holistic dietary pattern. Metabolomics and proteomics are high- throughput methods for efficient measurement of compounds in biological specimens. The metabolome reflects the breakdown products of food that is consumed and can represent not only food items and their components but also dietary patterns. The proteome represents biological function and activity, which complements the metabolomic profile. We propose to conduct untargeted metabolomics and proteomics for the discovery of novel biomarkers of the DASH diet as well as biomarkers of DASH diet mediated blood pressure reduction. Findings will be replicated in two independent study populations and validated by using targeted, quantitative assays of candidate biomarkers. This cost-effective proposal leverages the existence of study data and biospecimens in the NHBLI BioLINCC repository as well as existing omics data. The study team is led by a K01-funded, early stage investigator who has been trained in metabolomics of diet and chronic disease outcomes. Study team members are established, senior investigators who have a history of collaboration with the Principal Investigator and complementary expertise in nutritional biochemistry, untargeted metabolomics and proteomics platforms, laboratory methodology, biostatistics, dietary intake, blood pressure, and deep knowledge of the study populations to be investigated. This proposed research will advance the current methods for assessing dietary intake and will provide insights for clinically-important, diet- modifiable metabolic pathways.