MAESTRO 13 for Professor Stefan Chłopicki

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.

OPUS 21 NCN: What do we not know about breast cancer?

In the last edition of the OPUS competition announced by the National Science Center in Krakow, Dr. Marta Smęda received funding for research on breast cancer issues. In her project, she will examine Breast cancer metastasis-induced endothelial-mesenchymal transition alongside ageing; implications for therapy.

Ageing results in progressive vascular dysfunction. The cornerstone mechanism that may lay behind age- and/or cancer-dependent deterioration of endothelial function is mesenchymal transformation of endothelial cells (EndMT) that may determine the endothelium status and, thus, the outcome of breast cancer. Progression of EndMT and its consequences in ageing remain largely unknown. Both cancer and ageing alter platelet phenotype. Therefore, although circulating platelets of healthy individuals support endothelium function, age- and/or cancer-altered platelets may act in the opposite way: drive EndMT and disrupt endothelial barrier.

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OPUS 21 NCN for Jakub Dybaś, Ph.D

417 projects will be financed in the OPUS 21 call announced by the National Investment Science Center which is 18% of all submitted applications. One of them is a project by Ph.D Jakub Dybas, entitled In search of the unexplored aspects of ferric heme protein-dependent regulation of nitric oxide signaling in the erythrocyte and vessel wall.

Nitric oxide (NO) is one of the major transmitters involved in maintaining of the proper vascular homeostasis in the circulatory system through contribution in lowering blood pressure and vasodilating smooth muscle cells. Bioactivity of NO is controlled, among the others, by heme proteins which participate in both – promoting and suppression of NO vasodilating property. Significance of heme proteins depend on the oxidation state of porphyrin-bound iron ion – ferrous heme proteins (with Fe2+ iron ion) scavenge and attenuate NO while ferric heme proteins (with Fe3+ iron ion) interact reversibly with NO allowing its diffusion and permitting bioactivity. However, precise role of ferric heme proteins remain elusive due to the lack of methodology allowing for simultaneous detection, differentiation and spatial distribution characterization of ferrous and ferric heme proteins. The aim of this project is to design the unique imaging methodology based on resonance Raman (rR) spectroscopy allowing examination of unexplored aspects of NO bioactivity regulation by ferric heme proteins and better understanding of mechanisms regulating NO signaling in erythrocyte and vessel wall.

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