The National Science Center in Krakow has published the results of the MAESTRO 13 competition. The thirteenth edition turned out to be lucky for the Director of the Jagiellonian Centre for Experimental Therapeutics (JCET), Professor Stefan Chłopicki, who received funding for the project: Metabolic reprogramming in age-dependent endothelial dysfunction and vascular stiffness; novel mechanism of “inflamm-ageing”.
Ageing is the major risk factor of various diseases including cardiovascular diseases. Chronic, sterile, low-grade inflammation observed in older organism that have been recently named “inflamm-ageing”, results in accelerated development of endothelial dysfunction and large arteries stiffness. These two phenotypes; systemic endothelial dysfunction and increased stiffness of large arteries, can be measured in clinical conditions, and predict morbidity and mortality of cardiovascular diseases. Accordingly, the improvement in endothelial function and artery stiffness can have therapeutic effects. However, mechanisms involved in inflamm-ageing are not clear.
In the present project, we hypothesize that accelerated age-dependent dysfunctional vasculature in E3L.CETP mice might be explained by vascular metabolic reprogramming that could contribute to vascular inflamm-ageing and subsequently to persistent vascular inflammation, enhanced susceptibility of vascular wall to inflammatory insults, and to endothelial dysfunction and arterial stiffness. We aim to characterize metabolic signature of inflamm-ageing in murine models, and in particular to define the mechanisms and importance of metabolic reprogramming in the development of age-dependent endothelial dysfunction in large arteries and in coronary microcirculation, as well as in arterial stiffness. Project will be based on interdisciplinary, state-of-the art methodologies including e.g.; Magnetic Resonance Imaging – MRI to assess endothelial function in vivo in mice, microfluidic device to characterize in vitro primary endothelial cells isolated from mice, and targeted and non-targeted metabolomics to define metabolic pathways of dysfunctional endothelium and vascular wall ex vivo.