JCET

In the 20th edition of the PRELUDIUM competition announced by the National Science Center in Krakow, Agnieszka Karaś, M.Sc., is one of the winners, who is pursuing her doctorate in the laboratory of the Jagiellonian Center for Experimental Therapeutics. The subject of the distinguished project is: “The role of lactate dehydrogenase A in development of endothelial dysfunction in murine model of heart failure”.

The aim of this project is to evaluate the link between vascular metabolism and endothelial dysfunction during the development of heart failure. Heart failure (HF) is currently a leading cause of mortality worldwide, moreover, in Poland, the morbidity and mortality of HF are one of the highest in Europe. Interestingly, systemic endothelial dysfunction is observed in patients even with mild HF and is an important factor predicting poor patient outcome and increased risk of cardiac death. Endothelium, the single layer of cells lining the interior surface of blood vessels, plays a crucial role in maintaining healthy vessel function. To date, the mechanisms of endothelial dysfunction development in HF are not clear. We hypothesise that alterations in cellular bioenergetics in the vessel wall may contribute to vascular pathology in the progression of HF. Therefore, this study is set out to understand the connection between endothelial dysfunction and metabolic changes focusing on the role of lactate dehydrogenase A (LDHA), an enzyme responsible for the production of lactate, which is not only an energy source but also a crucial regulatory factor. This project will be performed using a murine model of HF. Results of this study will shed new light on vascular pathophysiology in HF and may contribute to novel therapeutic strategies improving patient prognosis.

On September 27, 2021, the National Science Center in Krakow announced the results of the Weave-UNISONO competition. The first grant on sepsis research will go to the Director of JCET, Professor Stefan Chłopicki.

Project entitled “Specific pathomechanisms of aging-related endothelial dysfunction in sepsis: investigation of mechanisms and experimental therapy” will be carried out by the team of prof. Chłopicki at the Jagiellonian Center for Experimental Therapeutics (JCET), in cooperation with the team of prof. Csaba Szabo from the Swiss University of Friborg. The project should shed new light on the pharmacotherapeutic mechanisms responsible for age-worsened endothelial dysfunction in sepsis. This topic is an important medical challenge as there is as yet no effective pharmacological approach to treating cardiovascular shock and multi-organ damage in sepsis.

Results

The results of the SONATA 16 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 PhD Grzegorz Kwiatkowski: “Impairment of coronary microcirculation in a mouse model of a heart failure“. The research will be carried out at the interdisciplinary laboratory of the Jagiellonian Centre for Experimental Therapeutics (JCET).

• Budget: PLN 1 462 962
• Implementation period: 36 months

In this project we aim to apply new protocols using advanced Magnetic Resonance Imaging methods to directly and indirectly observe changes in microvascular status occurring in coronary microcirculatory system and the corresponding impairment of the cardiac blood flow supply (so-called perfusion) using a murine model of heart failure. For this purpose, we plan to use a special breed of mice that over their life-span develop a cardiac impairment which is very similar to what we observe in human patients with congestive heart failure. We plan to probe the changes in coronary microcirculation during the whole progression of heart failure in animals and later to use the newly acquire knowledge to assess the effect of pharmacotherapy with several medication groups, commonly used to treat heart failure in humans.

The results of the OPUS 20 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 PhD Anna Bar: “LDL-mimetic liposomal contrast agent for MRI-based detection of increased endothelial permeability in the early phase of endothelial dysfunction in vivo“. The research will be carried out at the interdisciplinary laboratory of the Jagiellonian Centre for Experimental Therapeutics (JCET).

• Budget: PLN 2 496 000
• Implementation period: 48 months

The overall aim of this project is: firstly, to develop optimized MRI-based methodology for the endothelial permeability assessment in murine models in vivo and secondly to use this optimized method to characterize endothelial permeability changes induced by disease development and in response to pharmacotherapy.