JCET is a new unit of the Jagiellonian University, designed to develop experimental pharmacotherapy of lifestyle diseases and endothelium-targeted therapeutics in particular, as well as to develop the collaboration with industry partners in this field.

JCET is based on the collaboration of three parties Jagiellonian University (project leader), Lodz University of Technology and Henryk Niewodniczański Institute of Nuclear Physics Polish Academy of Sciences in Kraków. Those three partners form a comprehensive research infrastructure. Scientific Teams directly involved in JCET activities originate from four Faculties of the Jagiellonian University (Medicine, Pharmacy, Chemistry aswell as Biochemistry, Biophysics and Biotechnology), from the Institute of Radiation Technology (Faculty of Chemistry of the Lodz University of Technology) and from the Department of Magnetic Resonance Imaging (Institute of Nuclear Physics of Polish Academy of Sciences in Kraków).

The newly created JCET laboratories consist of the following complementary units: Laboratory of Experimental Pharmacology of Endothelium, Laboratory of Analytics and Pharmacokinetics, Laboratory of Molecular Pharmacology of Endothelium, Laboratory of Raman Spectroscopy, Laboratory of EPR Spectroscopy and the Animal Facility. JCET laboratories located in the Life skiego) closely cooperate with satellite JCET units such as: the Laboratory of Chemical Synthesis located within the Lodz University of Technology, the Laboratory of In vivo Imaging located within Nuclear Physics Institute of Polish Academy of Sciences in Kraków and the Laboratory of Clinical Pharmacology of Endothelium located within the University Hospital of the II Chair of Internal Medicine of Jagiellonian University Medical College.

The major goal of JCET activity and its interdisciplinary research is to develop novel endothelium-targeted therapeutics. Therefore the major JCET activities involve studies on synthesis, mechanisms of pharmacological activity, pharmacokinetic profile, metabolites and assessment of therapeutic properties of original chemical compounds (natural and synthetic), whichwould eventually lead to the introduction of the selected chemical compounds (potential drugs) into the preliminary phase of clinical trials.

The specialization within the area of vascular pharmacology and search for novel endothelium-targeted therapeutics is a distinctive feature of JCET research activities. One of the important goals of JCET is the development of a unique panel of assays, which would comprehensively evaluate the effects of chemical compounds on endothelium and blood vessels. Such endothelial profiling, being developed in JCET, will allowthe search and validation of innovative pharmacotherapeutic mechanisms of endothelium and vascular wall.

On the other hand, endothelial profiling assays will serve the evaluation of the vascular safety of the chemical compounds – the potential drugs being developed by JCET or JCET partners.

„In the pharmacology of endothelium everything is new. (…)
Old, beaten tracks are secure, but the newly discovered ones areinteresting”.

Ryszard Gryglewski

Current understanding of endothelial function and the role of endothelial dysfunction in cardiovascular diseases provides the rational basis for the development of a novel field in pharmacology – pharmacology of endothelium. Although it focuses on the treatment of vascular endothelium and vascular wall it is therapeutically applicable to a vast range of diseases, such as atherosclerosis, and vascular complications thereof (e.g. myocardial infarction), heart failure postoperative vascular complications, pulmonary hypertension, microangiopathies of neurodegenerative diseases and many others.

In fact, searching for effective endothelium-targeted therapeutics may also bear new therapeutic opportunities for prevention and treatment of diseases such as liver steatosis, chronic liver inflammation, diabetes and cancer metastasis that still represent unmet medical needs.

Indeed, drugs, which inhibit endothelial vasoprotective mechanisms or directly promote the development of endothelial dysfunction, may cause serious cardiovascular complications. A few promising drugs that have been recently introduced into clinical trials or into the market turned out to be detrimental to the vessel wall. It resulted in the suspension of clinical trials in which they were tested and in the withdrawal of drugs already introduced into clinical use. Thus there is a strong need for the development of novel and effectivemethods for preclinical drug testing thatwould focus on specialized evaluation of the effect of chemical compounds on endothelium (endothelial profiling).

targeted therapeutics opens new therapeutic possibilities for the treatment of many diseases. On the other hand, endothelial profiling seems to be essential for a full preclinical assessment of drug safety, and this applies to all potential drugs, regardless of their original therapeutic indication.

Accordingly, themajor directions of JCET activities are interdisciplinary research and the development of novel endothelium-targeted therapeutics and endothelial profiling of various compounds beeing develop as drug candidates.

A far-reaching goal of JCET is broadening its unique specialization in the field of the pharmacology of endothelium and vascularwall based on the unique research instrumentation and the results of the ongoing strategic research project of JCET (see p.31) to become a recognized academic centre fostering the development of endothelial and vascular pharmacology.

JCET faces ambitious goals and interesting perspectives. The coming years will show how JCET will cope with these challenges.

Stefan Chłopicki