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的威胁之一--心血管--的一个可改变的危险因素 疾病。阻止高血压的饮食方法(DASH)饮食模式是一个高- 高质量的饮食，富含水果、蔬菜和低脂乳制品，低钠、饱和脂肪和 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性疾病。现有的饮食摄入量生物标志物很少 代表单一的营养素，而不是整体的饮食模式。代谢组学和蛋白质组学是高度- 生物样品中化合物的有效测量的通过量方法。代谢物 反映所消费的食品的细分产品，不仅可以代表食品及其产品 不仅有营养成分，还有饮食模式。蛋白质组代表生物功能和活性，它 补充了新陈代谢的特征。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饮食介导性血液的生物标志物的发现 压力降低。研究结果将在两个独立的研究群体中重复，并通过使用 对候选生物标记物进行有针对性的定量分析。这一具有成本效益的建议充分利用了 NHBLI BioLINCC库中的研究数据和生物标本以及现有的组学数据。这项研究 团队由K01资助的早期研究人员领导，他接受过饮食和慢性疾病代谢组学方面的培训 疾病后果。研究团队成员已经建立，高级调查人员有 与首席研究人员合作并补充营养生物化学方面的专业知识， 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，以及对待调查研究人群的深入了解。这项拟议的研究将 推进当前评估膳食摄入量的方法，并将为临床上重要的饮食- 可改变的代谢途径。

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.