Project 2
Metabolic drivers of hypertension: focus on the microcirculation
Objectives:
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.
Methodologies:
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.
Requirements:
- Qualifications: Master of Science in Health Sciences, Biomedical Sciences, Medicine, Biology, Computational Biology or a related field.
- Experience: Epidemiology, Big data analysis, Vascular biology.
- Knowledge & skills: Knowledge of vascular biology, hypertension, metabolomics. Good communication skills and analytical skills are essential.
- Abilities: Independent; prepared to take on challenging aims. Organising and prioritising own work and organising research within the project timetable are essential.
- Attitude and disposition: Highly collaborative, dedicated researcher who thrives in an ambitious academic environment, Internationally oriented.
- Other circumstances: Willingness to work flexibly in order to achieve project demands and targets as agreed with the supervisor. Able to travel to workshops and collaborating labs within EU.