Department of Neuro-cardiovascular Interactions

Department of Neuro-cardiovascular Interactions is focused on signaling pathways that may affect different mechanisms of the cardiovascular system by central and sympathetic regulations and vice- versa, on the analysis of metabolic processes in the heart and vessels that may affect both central nervous system and sympathetic autonomic nervous system. In the framework of the clinical practice outputs, the department is focused on monitoring of drugs and substances, in particular the polyphenolic substances, that determine the levels of nitric oxide and reactive oxygen species in cardiovascular and metabolic disorders. 

Department`s center of attention is experimental model of myocardial infarction in both normotensive and hypertensive rats. We study the effect of NO and CO donors, STAT1 and ISG15 inhibitors, as well as other substances on the size and area of myocardial infarction and accompanying pathophysiological changes.  

Concerning metabolic disorders that are commonly accompanied with neurological and psychiatric diseases, the aim of our study is to gain new knowledge on the crosstalk of metabolic factors and neurogenic signaling in the pathophysiology of depression and schizophrenia in animal models. 

Recently, the department is devoted to the research of targeted therapy based on preparation, analysis, and monitoring of active antihypertensive agents and substances affecting lipid metabolism bound to a polymeric and/or magnetic nanoparticles. 

The department in cooperation with material research analyzes the biocompatibility of magnesium implants for clinical use.

 

Head:

doc. RNDr. Oľga Pecháňová, DrSc.

tel.: +421 2 3229 6020

e-mail: olga.pechanova@savba.sk

 

Vice-head:

RNDr. Martina Cebová, PhD. 

 

Researchers:

MVDr. Andrej Barta, PhD. 

MUDr. Pavol Janega, PhD. 

RNDr. Jana Klimentová, PhD.

MUDr. Ján Lakota, CSc. 

doc. MUDr. Ján Lietava, CSc. 

MUDr., RNDr. Ľudovít Paulis, PhD. 

RNDr. Stanislava Vranková, PhD. 

 

PhD. students:

Mgr. Jakub Benko

MSc. Ezgi Dayar

Mgr. Mária Galšneiderová

 

Research assistant:  

Jana Peťová

 

Undergraduate student:

Katarína Andelová (Faculty of Natural Sciences, Commenius University Bratislava) 

 

The most important publication in last 5 years 

CEBOVÁ, Martina – KLIMENTOVÁ, Jana – JANEGA, Pavol – PECHÁŇOVÁ, Oľga. Effect of bioactive compound of Aronia melanocarpa on cardiovascular system in experimental hypertension. In Oxidative Medicine and Cellular Longevity, 2017, vol. 2017, article ID 8156594, 8 p. (4.593 – IF2016, Q1). 

LAKOTA, Ján – VULIĆ, Radivojka – DUBROVČÁKOVÁ, Mária – TYČIAKOVÁ, Silvia. Sera of patients with spontaneous tumour regression and elevated anti-CA I autoantibodies change the gene expression of ECM proteins. In Journal of Cellular and Molecular Medicine, 2017, vol. 21, no. 3, p. 543-551. (4.499 – IF2016).  

VRANKOVÁ, Stanislava – BARTA, Andrej – KLIMENTOVÁ, Jana – DOVINOVÁ, Ima – LÍŠKOVÁ, Silvia – DOBEŠOVÁ, Zdena – PECHÁŇOVÁ, Oľga – KUNEŠ, Jaroslav – ZICHA, Josef. The regulatory role of nuclear factor kappa B in the heart of hereditary hypertriglyceridemic rat. In Oxidative medicine and cellular longevity, 2016, vol. 2016, article ID 9814038, 6 p. (4.492 – IF2015). 

PECHÁŇOVÁ, Oľga – VARGA, Zoltan V. – CEBOVÁ, Martina – GIRICZ, Zoltan – PACHER, Paul – FERDINANDY, Peter. Cardiac NO signalling in the metabolic syndrome. In British Journal of Pharmacology, 2015, vol. 172, no. 6, p. 1415-1433. (4.842 – IF2014). 

ŠIMKO, Fedor – PECHÁŇOVÁ, Oľga – KRAJČIROVIČOVÁ, Kristína – MATUŠKOVÁ, Jana – PELOUCH, Václav – ADAMCOVÁ, Michaela – PAULIS, Ľudovít. Effects of captopril, spironolactone, and simvastatin on the cardiovascular system of non-diseased Wistar rats. In International Journal of Cardiology, 2015, vol. 190, p. 128-130. (4.036 – IF2014).

 

International collaborations

Department of Pharmacology and Pharmacotherapy, Semmelweis University Budapest, Hungary 

Research cooperation is focused on miRNA identification in endogenous cardioprotection in an experimental model of myocardial infarction. 

 

Faculty of Medical Sciences, University of Kragujevac, Serbia 

Research cooperation is focused on the monitoring of some cardiovascular and neurophysiological correlates as well as on the education. Dr. Pecháňová served as visiting-professor at Kragujevac University.  

 

Charité-University Medicine, Berlin, Nemecko     

Research cooperation resulted in the establishment of a joint workplace with ideas to cooperate on the analysis of mechanisms involved in activation of the RAAS.

 

Current projects

 

Effects of nanoencapsulated simvastatin on cardiovascular system in experimental metabolic syndrome 

Project leader: Oľga Pecháňová 

Project number: APVV-14-0932 

Duration: 1.7.2015 / 30.6.2019 

 

High level of cholesterol in the blood increases the risk of heart and vascular diseases. Simvastatin reduces cholesterol production in the liver thus reduces the blood cholesterol level. Long-term use of statins has been associated with the occurrence of side effects. In particular, the statin side effect include mainly inhibition of the endogenous synthesis of CoQ10 – a basic cofactor for ATP synthesis and paradoxically activation of PCSK9 – an important enzyme for the synthesis of LDL-cholesterol. The project aims to increase the bioavailability of simvastatin in the liver, thus reducing the daily dose and consequently to prevent the reduction of CoQ10 levels as well as to block the activation of PCSK9. In order to achieve this aim, nano-encapsulated simvastatin together with nano-encapsulated CoQ10 or PCSK9 inhibitor, or in the polymer with antioxidant properties will be prepared, tested and applied. This ensures a targeted transport of simvastatin to the liver simultaneously with CoQ10, or inhibitor of PCSK9, or simultaneous increase in antioxidant capacity. The project may uncover new possibility of using nanocarriers for the treatment of metabolic and cardiovascular diseases.  

 

The effect of STAT1 and ISG15 inhibitors on biochemical and morphological parameters in experimental myocardial infarction 

Project leader: Martina Cebová  

Project number: 2/0170/17  

Duration: 1.1.2017 / 31.12.2019 

Myocardial infarction (MI) remains a major cause of morbidity and mortality throughout the world. Chronic ischemia leads to irreversible myocardial damage. Reperfusion of myocardium may potentially save myocardial function, paradoxically, this process causes further damage of the myocardium and apoptosis of cardiomyocytes along with upregulation of STAT1 and ISG15. Thus, it is important to study different molecules which may block or revers pathological processes in myocardial reperfusion injury following MI at different levels. Therefore, the aim of our study is to analyze the effects of STAT1 and ISG15 inhibitors on reperfusion injury in the experimental model of MI (ischemia-reperfusion injury after STEMI revascularization) and determination of pathophysiological changes in this process. 

 

Effect of Cornus mas L. lyophilisate on cardiometabolic and inflammatory risk markers in experimental metabolic syndrome 

Project leader: Ján Lietava  

Project number.: VEGA 2/0137/16 

Duration: 1.1.2016 / 31.12.2018 

Functional food represents important alternative and complementation in the therapy and prevention of atherosclerosis, its risk factors and clinical complications. Cornelian cherry (Cornus mas L.) (CC) demonstrated high antioxidative potential with pronounced decrease of inflammatory markers and reduction of oxidative stress verified after inducted damage to liver, kidney, DNA in experimental studies. From clinical aspect is advantageous decrease of glycemia and increase of insulin (on level of glibenclamid effect) as well as favourable effect of lipid spectrum (comparable with lovastatin). Limitation of published studies is use of imprecisely defined cultivars of Cornus mas with different contents of active compounds. The studies also did not followed blood pressure as classic risk factor and homocysteine mediated modulation of DNA methylation as newer one, what is the main topic of this study on experimental metabolic syndrome model using lyophilisate of precisely defined Cornus mas cultivars. 

 

Protection of hypertensive and failure heart by I(f) channel blocker ivabradin: comparison with ACE inhibition and melatonin 

Project leader: Fedor Šimko 

Project leader at CEM SAS, INPP: OľgaPecháňová 

Project number: VEGA 1/0071/15 

Duration: 1.1.2015/31.12.2018 

The aim of the project is to monitor the effect of ivabradine I (f) channel blocker with concomitant captopril and melatonin administration on cardiometabolic parameters and nitric oxide synthase activity and its individual isoforms in rats with L-NAME-induced hypertension.  

 

Protective effect of NO and CO donors in experimental myocardial infarction with hypertensive complications 

Project leader: Oľga Pecháňová 

Project number: VEGA 2/0195/15 

Duration: 1.1.2015 /  31.12.2018 

Myocardial infarction (MI) is one of the leading causes of death in humans. While there is not always easily identifiable first pathogenic noxa, MI is characterized by ischemia, chronic inflammation and tissue degeneration. MI prognosis is conditioned by a series of risk factors, among these is the hypertension, which worsens the prognosis of MI by inducing a burden of oxidative and inflammatory mediators released within the heart. Therefore, studies with molecules possessing multiple activities and thus capable of blocking or reversing the pathological progress of hypertension and MI are needed. The signalling molecules nitric oxide (NO) and carbon monoxide (CO) could also be part of this strategy, since both have been shown to decrease blood pressure and protect the heart at different levels. Thus, we aim to study the effect of NO and CO donors on experimental MI and accompanying pathophysiological changes. This approach may ultimately increase efficacy in the clinical management of this disease. 

 

Crosstalk of metabolic factors and neurogenic signaling in experimental models of depression 

Project leader: Stanislava Vranková 

Project number: 2/0151/18 

Duration: 1.1.2018 / 31.12.2020 

Metabolic disorders like diabetes and obesity are commonly companied with neurological diseases and psychiatric disorders. Accumulating evidences indicated that cellular metabolic factors affect neurogenesis and have modulating effects on neurodegenerative disorders and psychiatric diseases including depression. On the other hand, as brain-derived neurotrophic factor (BDNF) contributes to the regulation of both synaptic plasticity and energy metabolism including feeding behavior, the neurotrophin has been recognized as a key target to clarify the relationship between metabolic and psychiatric disease. The aim of our study is to investigate the effects of high-fat diet (HFD) on disorder development in experimental models of depression. We will also explore whether the changes in neurobiology and behavior, can be positively influenced by 7,8-dihydroxyflavone (TrkB receptor agonist) treatment. Results of this project will contribute to elucidating the pathogenesis of depression and their treatment possibilities. 

 

Cardiovascular Effects of Nanoencapsulated Simvastain and Coenzyme Q10 in Experimental Hyperlipidemia (KANASTA) 

Project leader: Oľga Pecháňová 

Duration: 27.11.2015 / 26.11.2018 

The project is aimed to investigate the effect of nanoencapsulated simvastatin  together with CoQ10 on cardiovascular system. To our knowledge, no experimental or clinical study so far analyzed the effects of co-administration of nanoencapsulated simvastatin and CoQ10. 

 

Magnesium nanocomposites for biodegradable medical implants 

Project leader: František Simančík 

Project leader at CEM SAS, INPP: Oľga Pecháňová 

Duration: 1.11.2014 / 31.10.2017    

Project number: JRP 2014/5 

 


Past projects

 

EU-ROS: The European Network on Oxidative Stress and Redox Biology Research 

Project leader: Andreas Daibner (Johannes Gutenberg-Universität Mainz) 

Project leader at CEM SAS, INPP: OľgaPecháňová 

Duration: 1.6.2013/31.5.2016 

Project number: COST BM1203 

Description:

BM-1203 (EU-ROS) is a COST Action within the Biomedicine and Molecular Biosciences. Domain that covers all areas of medicine as practiced in Europe and basic, preclinical and clinical medical research developed to materialise the “bench to bedside” concept. COST is an intergovernmental framework for European Cooperation in Science and Technology, allowing the coordination of nationally-funded research on a European level. COST has a very specific mission and goal. It contributes to reducing the fragmentation in European research investments and opening the European Research Area to cooperation worldwide. As a precursor of advanced multidisciplinary research, COST plays a very important role in building a European Research Area (ERA). It anticipates and complements the activities of the EU Framework Programmes, constituting a “bridge” towards the scientific communities of emerging countries. It also increases the mobility of researchers across Europe and fosters the establishment of scientific excellence in the nine key domains.

 

Nitric oxide and brain redox status in a neurodevelopmental model of schizophrenia

Project no.: VEGA 2/0165/15,

Project leader: StanislavaVranková

Duration: 1.1.2015 – 31.12.2017

Description:

Schizophrenia is a severe mental disorder. Research suggests that an important role its pathophysiology may play the oxidative stress, i.e., redox imbalance in neurons of the central nervous system, leading to an impairment of brain development. This redox imbalance might be caused by an overproduction of nitric oxide (NO). Therefore, this project is focused at the role of NO in brain development. We will adopt a model of post-weaning social isolation of rats, which is an established neurodevelopmental model of schizophrenia. We will explore whether social isolation affects NO synthesis in the brain and whether NO production is linked with redox status of the brain tissue and schizophrenia-like behavioral alterations. We will also explore whether the changed in neurobiology and behavior, induced by isolation rearing, can be positively influenced by an antioxidative treatment. Results of this project will contribute to elucidating the pathogenesis of schizophrenia and its treatment possibilities.

 

Participation of HMGB1 in experimental myocardial infarction: cardioprotection vs. cardiac depression

Project no.: VEGA 2/0144/14,

Project leader: Martina Cebová

Duration: 1.1.2014 – 31.12.2016

Description:

Since many of proteins expressed during myocardial infarction (MI) could have either protective or harmful effects on function and structure of myocardium, it is important to analyze their activity as well as extensity of expression. High-mobility group box 1 (HMGB1) has been recently found as a nuclear protein released during the cerebral ischemic event and myocardial ischemia. The goal of this project is to determine the expression of HMGB1 after experimental MI and evaluate its effects. To analyze protective or by contrast damaging effects, the protein will be added or blocked, respectively. In case of protection, the optimal dose of added protein will be analyzed. In case of harmful effects, the protein will be blocked by both specific antibody or new Affibody molecules. The Affibody molecules are smaller and penetrate more deeply into the tissue. Thus, better protective effects may be expected. The results could be used to generate a drug characterized and optimized for subsequent clinical development.

 

Gasotransmitters: from basic science to therapeutic applications (ENOG: European Network on Gasotransmitters) 

Project leader: Andreas Papapetropoulos (University of Athens), 

Project leader at CEM SAS, INPP: OľgaPecháňová 

Duration: 1.5.2011/1.5.2015 

Project number: COST BM1005 

 

APVV – The effect of aliskiren loaded nanoparticles in experimental hypertension 

Project leader: Oľga Pecháňová  

Duration: 1.5.2011 / 31.10.2014  

Project no.: APVV-0742-10