The results of the SONATA 15 competition announced by the National Science Center (NCN) in Krakow are already known. The list of grants that have received funding also includes the project of Agnieszka Pełesz: “Novel strategies for pharmacological modulation of platelet-derived microparticles – effects on endothelium“. The research will be carried out at the interdisciplinary laboratory of the Jagiellonian Centre for Experimental Therapeutics (JCET).

• Budget: PLN 209 976
• Implementation period: 36 months

Currently, antiplatelet therapy plays an important role in prevention of arterial thrombosis and is thought also to be effective in preventing metastasis spread. Yet, we still have gaps in our understanding how antiplatelet agents affect cross-talk mechanisms between cells. The main intercellular communication mechanism of activated platelets involves extracellular vesicles transfer. Thus, extracellular vesicles act as important messengers in health and disease. Platelet-derived extracellular vesicles (PEVs) exhibit a wide range of pro-thrombotic, pro-inflammatory properties as well as can afford endothelial barrier protection. Therefore, it seems crucial to know how applied anti-platelet treatment affects modulation of PEVs release and their properties as messengers. To date, limited studies are available considering this topic, despite the fact that the repertoire of antiplatelet agents is still increasing. In particular, it is not known how antiplatelet agents modulate PEVs release and their effects on endothelial cells’ phenotype in healthy conditions as compared with atherosclerosis. In the current project, we will take the advantage of unique methods that have been developed in JCET for comprehensive endothelial profiling in vitro and ex vivo. Combining them with methods that will be developed within the frame of this project, we aim to broaden the knowledge about effects of antiplatelet pharmacology on extracellular vesicles release and function and their cross-talk with healthy endothelium or dysfunctional endothelium in atherosclerosis.

The latest results of the MINIATURE competition announced by the National Science Center (NCN) in Krakow have brought success to another scientist from the Jagiellonian Centre for Experimental Therapeutics (JCET) . PhD Grzegorz Kwiatkowski will carry out a project: “Non-invasive MRI assessment of microvascular nitric oxide synthase dysfunctionand permeability in the lung endothelium in a mouse model of a chronic heartfailure“.

• Budget: PLN 49,601
• Implementation period: 12 months

Endothelial dysfunction is a key characteristic of several cardiovascular diseases including diabetics, atherosclerosis and hypertension. In particular, global endothelial status holds a prognostic value in the development of heart failure. Several reports shown endothelial dysfunction developed over the course heart failure including impairment ofnitricoxide synthesis. Moreover, at the advanced stage of heart failure, the endothelial impairment was also observed in the lungs. There is, however, very little known on a relationship between lung microvascular endothelial status and heart failure progression. In particular, it is not known whether the lung endothelium exhibits adaptive or maladaptive mechanisms towards heart failure progression. The lung endothelium covers up to 30% of the total endothelial surface and as such is potentially an important treatment target.

Recent developments in the Magnetic Resonance Imaging offer novel, dedicated methods to study microcirculation but have not been yet applied to the lungs. We plan to employed state-of-the-art MRI protocols to characterize changes in the lung endothelium phenotype during the progression of heart failure in a mouse model of this disease.