The Early Stage Researcher (ESR) will be trained within the prestigious Marie Skłodowska-Curie Innovative Training Network MINDSHIFT (Mechanistic Integration of vascular aND endocrine pathways for Subtyping Hypertension: an Innovative network approach for Future generation research Training) and will perform the research project entitled "Metabolic drivers of hypertension: focus on the microcirculation" primarily at Maastricht University (The Netherlands) under the supervision of Dr Marleen van Greevenbroek, Dr Boy Houben and Prof Coen Stehouwer in close collaboration with the partner ESRs at UGLA, UAM and beyond.
The ESR will identify circulating metabolic drivers of obesity-associated microcirculatory dysfunction and hypertension. Data in the literature point at a role for lipids in e.g. nitric oxide bioavailability and endothelial/microvascular dysfunction. Other metabolic factors, including hormones and/or adipokines, can also affect endothelial/microvascular function. A comprehensive analysis of detailed metabolic information will be instrumental in the metabolic and endocrine subtyping of overweight/obese, hypertensive patients.
The ESR will use data of The Maastricht Study (currently available: n=3400), a deep-phenotyped, population-based cohort that is enriched for individuals with type 2 diabetes (Schram et al Eur J Epidemiol. 2014, Li et al, Am J Epidemiol. 2020). The Maastricht Study is expected to become one of the most extensive phenotyping studies in both the general population and type 2 diabetes participants world-wide.
The microvascular and metabolic phenotyping in The Maastricht Study allows detailed assessment of metabolic factors that pinpoint mechanisms in the development of microcirculatory dysfunction and hypertension. The microvascular phenotyping includes skin capillary density, heat-induced vasodilation, flowmotion, and retinal microvascular diameters and reactivity. The metabolomics data include 1H NMR metabolomics (~250 metabolites with focus on lipids and lipoproteins, fatty acids, amino acids and glycolysis/ketone bodies; https://nightingalehealth.com/science/biomarkers), complemented with biomarkers of inflammation, endothelial dysfunction, carbonyl stress and advanced glycation end-products. We will evaluate the associations of these circulating metabolites with microvascular dysfunction and hypertension, using regression analyses for individual metabolites and a systems biology approach for metabolic patterns. This enables us to determine to what extent the metabolites / metabolic patterns related to microvascular dysfunction overlap with those related to blood pressure (including 24h blood pressure variability) and whether they differ between subgroups, such as obese vs lean, and men vs women.
The ESR will additionally be trained in research groups of MINDHIFT network members in 1) isolated small vessel function (UGLA, Glasgow); 2) proresolvin lipid mediators effects on vascular cells (UAM, Madrid); 3) advanced microscopy and image analysis (Intelligent Imaging Innovations, London); 4) advanced data management (TMC Data Science, Utrecht).
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