PhD Kamil Przyborowski is the third laureate of the last edition of the SONATA competition, announced by the National Center of Science in Krakow on behalf of the Jagiellonian Centre for Experimental Therapeutics (JCET). Doctor Przyborowski will implement a project entitled Inhibition of protein disulfide isomerases as a strategy for reduction of prothrombotic state in atherosclerosis; therapeutic implications.

Antiplatelet treatment is a gold standard to combat atherothrombosis. Despite advances in antithrombotic therapy the cardiovascular diseases (CVDs), including myocardial infarction and stroke, are still the leading causes of death worldwide. Therefore, development of more effective and safe antithrombotic agents targeting new mechanisms is crucial. Protein disulfide isomerase (PDI) A1, PDIA3 or PDIA6 released from platelets and endothelium accelerate thrombus formation through effects on platelets and coagulation. Consequently, they are emerging as targets to inhibit thrombosis.

In the 17th edition of the SONATA 17 competition announced by the National Science Center in Krakow, PhD Agnieszka Kij is the second scientist from the Jagiellonian Centre for Experimental Therapeutics (JCET) which to receive funding for research . The Doctor Kij will run a project entitled “In the search of specific oxylipin fingerprint reflecting the development of endothelial dysfunction with the use of non-targeted and targeted lipidomics”.

Oxylipins are biologically active lipid mediators encompassing oxygenation products of polyunsaturated fatty acids (PUFAs) including arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Oxylipins such as AA-derived eicosanoids participate mainly in pro-inflammatory response (e.g., prostaglandins), with the exception of vasoprotective prostacyclin (PGI2). In recent years, an increasing attention has been paid to a novel class of AA-, EPA- and DHA-derived oxylipins referred as specialized pro-resolving mediators (SPMs; e.g., lipoxins LX, maresins MaR, resolvins RvE and RvD), that govern the resolution of inflammation and promote tissue regeneration. One can assume, that unresolved inflammation resulted from failed lipid mediator class switching from pro-inflammatory eicosanoids to SPMs can contribute to chronic vascular inflammation, and consequently to coronary and systemic endothelial dysfunction (ED). Despite the growing knowledge on lipid-dependent molecular mechanisms involved in endothelial dysfunction development, the pattern and time-frame of oxylipin alterations linked specifically to hyperlipidaemia- and age-induced coronary and systemic endothelial dysfunction, that could be helpful for early diagnosis, prevention and treatment of ED and cardiovascular diseases (e.g., atherosclerosis), have not been characterized.

In the 17th edition of the SONATA 17 competition announced by the National Science Center in Krakow, three scientists from the Jagiellonian Centre for Experimental Therapeutics (JCET) were among the winners. Today we present the assumption of the project of Dr. Eng. Marta Pacia, “Multimodal approach for a comprehensive assessment of (dys)functional endothelial phenotype in isolated blood vessels”.

Sodium-glucose co-transports 2 inhibitors (SGLT2-I) are a new generation of drugs for diabetes (including empagliflozin or dapagliflozin), however, their spectrum of action goes far beyond the systemic glucose reduction, and theirs protective effect on the ECs is postulated, both in hyperglycaemic conditions and in inflammatory state of the vasculature. Since the mechanism of action of SGLT2-I remains elusive so far, in this project I propose the development of a unique methodology aimed to uncover alterations of chemical, biological, nanostructural, and functional properties of activated/dysfunctional ECs in isolated blood vessels, which brings us closer to unravelling the mystery of how SGLT2-I actually work on the vascular wall. This first stage of the project includes the application of the developed research methodology to characterize the effect of SGLT2-I on inflammation- or hyperglycemia-activated endothelium, while the second stage includes the application of the developed research methodology to reveal the mechanisms of action of SGLT2-I and to verify the therapeutic efficiency of SGLT2-I to reverse endothelial dysfunction.