Identification of Metabolic Phenotypes and Systemic Biochemical Reaction Networks Associated with Human Blood Pressure

High blood pressure is an important component of metabolic syndrome and one of the most common modifiable risk factors for human cardiovascular disease and non-communicable disease. High blood pressure remains to be the leading cause for global disease burden and is estimated to attribute to 10.7 million deaths globally.
Different clinical and population-wide strategies have been in use to reduce high blood pressure such as to slow the rise of obesity, to increase physical activity, to reduce tobacco use and to change dietary patterns including the reduction of salt intake.
However, better knowledge of the effects of high blood pressure on human metabolism is needed to provide insight into the molecular mechanisms by which blood pressure is controlled. The human metabolic phenotype reflects the health status of an individual and is affected by genetic, environmental, dietary and gut-microbial variation.
I propose to use a metabolic phenotyping approach to discover biochemical compounds (metabolites) in urine related to blood pressure and associated dietary patterns, and to investigate how these potential clinical metabolic targets fit in the biochemical processes involved with the onset of high blood pressure and homeostatic regulation of blood pressure.

I aim to evaluate the relationship between the urinary metabolic profile and blood pressure, including the linkage with adiposity, salt intake and associated dietary patterns and map these in a holistic systems framework.
Objectives:
A) To uncover the metabolic signature of blood pressure by means of a Metabolome-Wide Association Study with control for confounding variables using 1H Nuclear Magnetic Resonance (NMR) spectroscopy and Direct Injection Mass Spectrometry (DIMS) data.
B) To identify novel associations between the intake of dietary nutrients and excretion of urinary metabolites to pinpoint dietary patterns associated with cardiometabolic risk.
C) To investigate the interdependence between cation (calcium, magnesium, potassium and sodium) and metabolite excretions with respect to renal function and (re-)absorption, and homeostatic regulation.
D) To map the pathways perturbed by high blood pressure, sodium consumption and dietary patterns, and assess the overlap with the metabolic and systemic signature of adiposity and other risk factors to reveal the integrated systems network of blood pressure.
Methodology: I propose to use the Metabolome-Wide Association Study paradigm on 24-hour urine samples measured with 1H NMR spectroscopy and DIMS, and enhance this by coupling multivariate statistical methods with the analysis of integrated systems metabolic reaction networks.
Outcomes: This work will improve the understanding of the molecular mechanisms underlying high blood pressure and define new potential starting points for the development of appropriate and comprehensive preventive and treatment strategies to address the increasing problem of blood pressure worldwide.