The GENERAL AIM of this proposal is to qualitatively advance knowledge on urinary metabolic phenotypes and biochemical pathways associated with the direct effect on blood pressure (BP) of high sodium (Na) intake and the inverse BP effect (BP reduction) of the DASH/OmniHeart- like eating pattern. To achieve this aim, we will identify and quantify key metabolites related to these contrasting BP influences, and use state-of-the-art chemometrics, statistical spectroscopy, computational network and pathway modeling tools to identify and map de novo pathways associated with Na-BP and DASH/OmniHeart-BP. We will then test and validate the INTERMAP derived metabolites and pathways using available data and samples from the INTERMAP China Prospective (ICP) Study, the Urinary Sodium Study (USS), and the OmniHeart Trial. The goal is to develop more focused and effective strategies for population- wide BP lowering through improved non-pharmacologic approaches, primarily nutritional, as well as to identify new targets for drug intervention. To our knowledge, this is the first investigation to identify urinary metabolites and associated pathways related to Na-BP and DASH/OmniHeart-BP, link these to dietary and other data, and with extensive validation in other cohorts, prospective and trial data.
This study is desiged to take advantage of a unique opportunity to further delineate, differentiate and quantify biological pathways that relate to either increased or decreased blood pressure levels. The proposed focus is on urinary metabolites associated with dietary sodium (Na), DASH/OmniHeart diet and blood pressure. These findings can help identify targets for dietary and/or drug interventions aimed at effective prevention/treatment of hypertension, a major population-wide independent established risk factor for cardiovascular disease.
|Chekmeneva, Elena; Dos Santos Correia, Gonçalo; Gómez-Romero, María et al. (2018) Ultra-Performance Liquid Chromatography-High-Resolution Mass Spectrometry and Direct Infusion-High-Resolution Mass Spectrometry for Combined Exploratory and Targeted Metabolic Profiling of Human Urine. J Proteome Res 17:3492-3502|
|Chan, Queenie; Loo, Ruey Leng; Ebbels, Timothy M D et al. (2017) Metabolic phenotyping for discovery of urinary biomarkers of diet, xenobiotics and blood pressure in the INTERMAP Study: an overview. Hypertens Res 40:336-345|