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

DASH 饮食和高血压生物标志物的发现、复制和验证

• 批准号: 10829021
• 负责人: Casey Marie Rebholz
• 金额: $ 16.38万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10829021
• 关键词: Adult; Atherosclerosis Risk in Communities; Biological; Biological Availability; Biological Markers; Blood; Blood Vessels; Body mass index; Cardiovascular Diseases; Cardiovascular system; Characteristics; Chronic Disease; Clinical Trials; DASH diet; Data; Disease Outcome; Dose; Elderly; Epidemiology; Event; Fat-Soluble Vitamin; Fibrosis; Funding; Gene Expression; Goals; Health; Heterogeneity; Hormonal; Hypertension; Incidence; Inflammation; Intake; Knowledge; Link; Measures; Metabolic Pathway; Metabolism; Modernization; Observational Study; Outcome; Participant; Pathway interactions; Phenotype; Physiological; Plasma; Plasma Proteins; Proteins; Proteome; Proteomics; Race; Randomized, Controlled Trials; Recurrence; Regulation; Renal function; Renin-Angiotensin-Aldosterone System; Research; Research Personnel; Role; Serum; Source; Specimen; Up-Regulation; Urine; Visit; Vitamin D; Vitamin D supplementation; biomarker discovery; biomarker panel; biomarker validation; bone health; candidate marker; cardioprotection; cardiovascular disorder risk; cardiovascular health; cell growth; cohort; cost effective; dietary; experience; follow-up; gene product; high throughput technology; insight; metabolome; metabolomics; middle age; mortality; multiple omics; novel; novel marker; pre-clinical; predictive marker; prospective; protein biomarkers; sex

ABSTRACT Preclinical and observational evidence supports a cardioprotective role of vitamin D. However, vitamin D supplementation in randomized controlled trials has failed to reduce cardiovascular events or cardiovascular mortality. Characterizing metabolites and proteins associated with vitamin D supplementation, assessing their associations with cardiovascular disease, and examining sources of heterogeneity may help to elucidate mechanisms underlying the epidemiological associations and yield insights into the discrepant null findings in clinical trials. While serum 25(OH)D is commonly measured to assess vitamin D status and its association with disease outcomes, it does not directly reflect biologically available vitamin D or its functions in the body. High-throughput technologies can identify thousands of metabolites and proteins in blood and urine, which may provide a more comprehensive understanding of vitamin D metabolism than serum 25(OH)D. We propose to investigate novel biomarkers of vitamin D supplementation in the Atherosclerosis Risk in Communities Study (ARIC) using untargeted metabolomic and proteomics, as well as examine prospective associations between vitamin D-related metabolites and proteins with cardiovascular outcomes. This cost-effective proposal leverages existing omics data in a richly phenotyped cohort of black and white older adults with validated cardiovascular outcomes. Untargeted metabolomics of both serum and urine, and untargeted plasma proteomics, have already been analyzed using specimens collected at ARIC visit 5. Our multi-omic approach maximizes opportunities for biomarker discovery, as well as exploration of how these biomarkers vary according to participant characteristics including sex, race, and body mass index. The study team is led by an R01-funded investigator with extensive experience analyzing metabolomics and proteomics of dietary exposures and chronic disease outcomes. The proposed research will advance knowledge of vitamin D metabolism and characterize pathways through which vitamin D supplementation may promote cardiovascular health.

抽象的 临床前和观察证据支持维生素D的心脏保护作用。但是， 随机对照试验中补充维生素D未能减少心血管事件 或心血管死亡率。表征与维生素D相关的代谢产物和蛋白质 补充，评估他们与心血管疾病的关联，并检查 异质性可能有助于阐明流行病学关联和 在临床试验中对差异无效发现的见解。而血清25（OH）D通常是 测量以评估维生素D状况及其与疾病结局的关联，它不会直接 反映生物可用的维生素D或其在体内的功能。高通量技术可以 识别血液和尿液中成千上万的代谢产物和蛋白质，这可能会提供更多 比血清25（OH）d的维生素D代谢的全面了解。我们建议 研究在动脉粥样硬化风险中补充维生素D的新型生物标志物 社区研究（ARIC）使用未靶向的代谢组学和蛋白质组学，并检查 维生素D相关的代谢物与蛋白质与心血管的前瞻性关联 结果。这项具有成本效益的建议利用了现有的OMICS数据 黑白老年人具有经过验证的心血管结局。未靶向的代谢组学 血清和尿液，以及未靶向的血浆蛋白质组学，已经使用 在ARIC访问5上收集的标本5。我们的多摩变方法最大化生物标志物的机会 发现以及探索这些生物标志物如何根据参与者特征变化 包括性别，种族和体重指数。研究团队由R01资助的调查员领导 分析饮食暴露和慢性的代谢组学和蛋白质组学的丰富经验 疾病结果。拟议的研究将提高对维生素D代谢的了解和 表征维生素D补充可以促进心血管健康的途径。

项目成果

Plasma Metabolites Associated with a Protein-Rich Dietary Pattern: Results from the OmniHeart Trial.

• DOI: 10.1002/mnfr.202100890
• 发表时间: 2022-03
• 期刊: Molecular nutrition & food research
• 影响因子: 5.2
• 作者: Kim H;Lichtenstein AH;White K;Wong KE;Miller ER 3rd;Coresh J;Appel LJ;Rebholz CM
• 通讯作者: Rebholz CM

Metabolomic Profiles Associated With Blood Pressure Reduction in Response to the DASH and DASH-Sodium Dietary Interventions.

• DOI: 10.1161/hypertensionaha.123.20901
• 发表时间: 2023-07
• 期刊: HYPERTENSION
• 影响因子: 8.3
• 作者: Kim, Hyunju;Appel, Lawrence J.;Lichtenstein, Alice H.;Wong, Kari E.;Chatterjee, Nilanjan;Rhee, Eugene P.;Rebholz, Casey M.
• 通讯作者: Rebholz, Casey M.

Urine Metabolites Associated with the Dietary Approaches to Stop Hypertension (DASH) Diet: Results from the DASH-Sodium Trial.

• DOI: 10.1002/mnfr.202000695
• 发表时间: 2021-03
• 期刊: Molecular nutrition & food research
• 影响因子: 5.2
• 作者: Kim H;Lichtenstein AH;Wong KE;Appel LJ;Coresh J;Rebholz CM
• 通讯作者: Rebholz CM

Association Between Ultraprocessed Food Consumption and Risk of Incident CKD: A Prospective Cohort Study.

• DOI: 10.1053/j.ajkd.2022.03.016
• 发表时间: 2022-11
• 期刊: American journal of kidney diseases : the official journal of the National Kidney Foundation

Serum Metabolomic Markers of Dairy Consumption: Results from the Atherosclerosis Risk in Communities Study and the Bogalusa Heart Study.

乳制品消费的血清代谢标志物：社区研究和博加卢萨心脏研究中动脉粥样硬化风险的结果。

• DOI: 10.1016/j.tjnut.2023.08.001
• 发表时间: 2023
• 期刊: The Journal of nutrition
• 作者: Bernard,Lauren;Chen,Jingsha;Kim,Hyunju;Huang,Zhijie;Bazzano,Lydia;Qi,Lu;He,Jiang;Rao,VarunS;Potts,KaitlinS;Kelly,TanikaN;Wong,KariE;Steffen,LynM;Yu,Bing;Rhee,EugeneP;Rebholz,CaseyM
• 通讯作者: Rebholz,CaseyM