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Institute for Heart Research

International projects

Mechanisms of radiation injury to the heart. Preventive drug treatment.
Mechanizmy poškodenia srdca radiáciou a možnosti medikamentóznej prevencie.
Program: Multilaterálne - iné
Project leader: D.h.c.,Prof., MUDr. Slezák Ján DrSc., FIACS
Duration: 1.1.2014 - 31.12.2017

Multidisciplinary analysis of the combined effects of thyroid hormones and n-3 polyunsaturated fatty acids in rats
Multidisciplinárna analýza kombinovaného vplyvu tyreoidnych hormonov a n-3 polynenasytených mastných kyselin u potkanov
Program: Medziakademická dohoda (MAD)
Project leader: RNDr. Tribulová Narcisa DrSc.
Annotation:Thyroid hormones (TH) play a crucial role in healthy organisms, but profound alterations of their levels can affect metabolic and signaling processes in different tissues. We will use hyper- and hypothyroid rats as “model of a diseased organism” and analyze whether and how n-3 PUFA long term administration will ameliorate TH-induced pathophysiological changes. We will investigate skeletal and cardiac muscle tissue remodeling, changes in serum lipids and in body fat distribution, key enzymes of TH metabolism, oxidative stress in the whole organism and within the cell. We will focus on myosin heavy chain composition, distribution and phosphorylation of connexin-43, cellular calcium handling, membrane anisotropy, mitochondrial functions and related signaling pathways including cell death and antioxidant defense. As n-3 PUFA possess multiple sites of potential action, we believe that our complex research will contribute to a better understanding of molecular mechanisms governing n-3 PUFA actions and to their more effective application in the prevention of pathological symptoms in man.
Duration: 1.1.2015 - 31.12.2017

EU-CARDIOPROTECT - Realising the therapeutic potential of novel cardioprotective therapies
Realizácia terapeutického potenciálu nových kardioprotektívnych terapií
Program: COST
Project leader: MUDr. Ravingerová Táňa DrSc., FIACS
Annotation:The proposed COST Action will set up a pan-European Research Network of leading experts in cardioprotection, to jointly develop new initiatives and new strategies for finding innovative and more effective approaches to cardioprotection and for optimizing the pre-clinical and clinical evaluation of new cardioprotective therapies, so as to improve their translation into the clinical setting for patient benefit. The COST Action will co-ordinate and strengthen European research in the field of cardioprotection and accelerate scientific progress through the dissemination and sharing of new therapeutic targets, among network members and industrial partners, thereby facilitating the discovery of new cardioprotective therapies. By utilizing the joint expertise of different European network members we will investigate factors which confound the efficacy of new cardioprotection therapies including comorbidities (such as age, diabetes, and hypertension) and co-medications (such as anti-platelet therapies, statins and beta-blockers). Finally, we will set up a European network of research centers for multi-center laboratory testing of new cardioprotective therapies using small and large animal models of acute IRI in order to select those therapies most likely to succeed in the clinical setting. All aspects of this COST Action proposal require a critical mass of partners across a wide geographic distribution across Europe in order to deliver the objectives outlined in this proposal. The discovery of novel signaling pathways and targets underlying cardioprotection both within and outside the cardiomyocyte (WG1 NEW TARGETS), and the testing of different combinations of cardioprotective therapy (WG2 COMBINATION THERAPY) requires investigators with different experience and expertise across Europe. The ability to test the effect of confounders of cardioprotection (WG3 CONFOUNDERS) requires the expertise of different partners in the different co-morbidities and testing of co-medications. Finally, the most important objective of this COST Action proposal, requires the setting up of a Europe-wide research network for (a) multicenter testing of novel cardioprotective therapies using small and large animal models (WG4 CONSORTIUM) and (b) testing of novel cardioprotective therapies in proof-of-concept clinical studies and optimization of multi-center clinical outcome cardioprotection studies. By definition this requires a critical mass of research partners distributed across Europe.
Duration: 19.10.2017 - 18.10.2021

Investigation of the mechanims involved in antiarrhythmic effects of melatonin
Skúmanie mechanizmov antiarytmických účinkov melatonínu.
Program: Bilaterálne - iné
Project leader: RNDr. Tribulová Narcisa DrSc.
Annotation:Cardiovascular diseases (CVD) are worldwide major cause of morbidity and mortality due to heart failure and incidence of malignant arrhythmias. Main risk factors of CVD are hypertension, diabetes, dyslipidemia, obesity, chronodisruption and stress. Aimed to prevent CVD and life-threatening arrhythmias it seems extremely important to investigate “pleiotropic” effects of endogenous candidate relevant to the CVD, i.e. neurohormone, melatonin. Neuro-humoral circadian rhythms are ‘chronically’ impaired and result in dys-synchrony of cellular cross talk in different tissues of individuals suffering from CVD. Lack of melatonin was repeatedly reported in patients with coronary heart disease. It appears that melatonin may serve as a new biomarker for a CVD risk. Melatonin in addition to its chrono-regulatory role exerts various “pleiotropic” actions: modulation of blood pressure and NO bioavailability, antioxidant, free radicals scavenging and anti-inflammatory effects, sympatholytic and anti-fibrotic potential and epigenetic regulatory function. Of note, previous experimental studies at both institutions showed clear-cut antiarrhythmic effect of melatonin in various pathophysiological conditions. Findings revealed that melatonin up-regulates myocardial connexin-43 (Cx43), protein of intercellular gap junction channels that are important for electrical impulse propagation and synchronization. Besides, melatonin modulates action potential duration suggesting its effect most likely on potassium and/or calcium channels. Nevertheless, there is a need to elucidate more in details the cellular and molecular mechanisms implicated in antiarrhythmic actions of melatonin
Duration: 1.5.2014 - 31.12.2017

Effect of pathological states on cardiac resistance against myocardial ischemia: study of molecular mechanisms and novel approaches to cardioprotection
Vplyv patologických stavov na odolnosť srdca voči ischémii myokardu: štúdium molekulárnych mechanizmov a nových možností kardioprotekcie
Program: Medziakademická dohoda (MAD)
Project leader: MUDr. Ravingerová Táňa DrSc., FIACS
Annotation:Previously, we showed a negative impact of civilization diseases (hypertension, metabolic disorders) on adaptive mechanisms in the heart and its survival under conditions of acute ischemia/reperfusion (I/R). Comorbidities and age- and gender-related changes blunt protective cell signaling of ischemic preconditioning (PC) leading to acceleration of necrotic and apoptotic processes, impaired function of mitochondria and energy production. The project is focused on the study of molecular mechanisms that alter innate cardioprotection in the diseased myocardium and on possibilities to reactivate its adaptive potential. We will explore effects of novel forms of PC, so called „remote“ PC (induced by limb ischemia) that are less technically demanding and can be used in clinical practice, e.g., in elder patients with acute myocardial infarction. Investigation of mechanisms of „remote“ PC will enable its pharmacological simulation, e.g., using pleiotropic (other than primary) effects of PPAR agonists or their combination with PC that can facilitate stimulatory effect on cardiac resistance against I/R.
Duration: 1.1.2015 - 31.12.2017


National projects

MEDMEX - Study of endogenous compensatory mechanisms effective against energy deficiency in pathologycally loaded myocardium: Innovative approaches in experimental cardioprotection.
Kompenzačné ochranné mechanizmy ako účinný nástroj voči zvýšenej energetickej deficiencii patologicky zaťaženého myokardu: Výhodná perspektíva v modernej experimentálnej kardioprotekcii.
Program: APVV
Project leader: Ing. Ferko Miroslav PhD.
Annotation:Research on field of compensatory mechanisms appears to be promising method for endogenous protection in pathologically loaded myocardium under condition of increased energy demands. The project aims to contribute to the knowledge in the field of experimental cardiology and point to new, alternative cardioprotective procedures against ischemia-reperfusion injury. It is necessary to study the protective signaling pathways, propose potential cardiomarkers and identify positive functional changes observed at the level of cardiac mitochondria and heart its self for comprehensive understanding of the onset and progression of mechanisms of endogenous myocardial protection leading to effective compensation against energy deficiency in ischemia/reperfusion injury. Several approaches utilize processes of endogenous protection to achieve cardioprotection, such as ischemic and pharmacological preconditioning, clinically applicable „remote“ ischemic preconditioning (RIP) as well as experimental streptozotocine-induced diabetes mellitus in acute state. Coexistence of several comorbidities (hypercholesterolaemia, hypertension) suppress mechanisms of cell signaling involved in protective effect of ischemic preconditioning that promotes necrotic and apoptotic processes in the myocytes during ischemiareperfusion challenge and also reduces energy production. With respect to bioenergetics and the role of mitochondria involved in the execution phase of cardioprotection as a common mechanism in various types of adaptive phenomena, the information is scarse up to date. It is expected that the project will help to characterize the changes caused by functional remodeling of the mitochondrial membrane, and provide a new and currently absenting information on regulation of mechanisms against increased enegetic demands resulting in myocardial survival.
Duration: 1.7.2016 - 30.6.2020

Bioenergetic aspects of myocardial protection by means of remote ischemic preconditioning. The role of cardiac mitochondria
Bioenergetické aspekty ochrany myokardu pomocou remote ischemického preconditioningu. Úloha srdcových mitochondrií
Program: VEGA
Project leader: Ing. Ferko Miroslav PhD.
Annotation:Any sufficiently strong challenge induced by physiological or pathological stimuli leads to myocardial changes that can be considered as abnormal. These changes partially reflect endogenous protective processes. Pathological stimuli triggering the endogenous protection are hypoxia, ischemia, diabetes mellitus and hypertension. Cardioprotective approaches involve pharmacological and ischemic preconditioning (IP) as well as clinically applicable form of IP, so called remote ischemic preconditioning (RIP). Numerous mechanisms of RIP induction and effects have been investigated. Still, the character of the signals from the site of RIP leading to target structures in the heart is not elucidated. Little is known also with respect to bioenergetics aspects and role of cardiac mitochondria in RIP induced cardioprotection. The aim of this project is to contribute to elucidation of the molecular mechanisms of RIP and role of mitochondria in the signaling processes of RIP and heart adaptation to hypoxia and ischemia.
Duration: 1.1.2015 - 31.12.2017

Hypoxia in the prevention of heart failure in rats and its influence in various stages of heart failure: Characteristics of functional, structural and molecular changes.
Hypoxia ako prevencia zlyhávania srdca potkana a jej vplyv v rôznych fázach zlyhávania: Charakteristika funkčných, štrukturálnych a molekulárnych zmien.
Program: VEGA
Project leader: Mgr. Farkašová Veronika PhD
Annotation:Ischemic heart disease and hypertension are major ailments leading to heart remodeling, cardiac hypertrophy, and subsequent heart failure (HF). Progression of HF depends not only on the extent of ischemic injury, but also on the presence of lifestyle risk factors. Cardioprotective adaptive interventions can slow the progression of cardiac hypertrophy to HF, but their effectiveness is adversely affected by cardiovascular comorbidities and by aging. The project aims are to study the possibility of reactivating adaptative potential in pathologically remodelled myocardium by modulating the intensity and timing of adaptive stimuli. We will examine the effects of intermittent hypoxia applied prior to the pathological stimulus and in various stages of development of hypertrophy and HF, focusing on functional and structural changes in the myocardium. We will aim to characterize the specific signaling pathways associated with the origin and development of HF and hypoxia-induced changes in intracellular signaling.
Duration: 1.1.2017 - 31.12.2019

Matrix-metalloproteinases, microRNAs and deformability of erythrocytes as a novel diagnostic and predictive biomarkers of heart failure
Matrix metaloproteinázy, microRNAs a deformabilita erytrocytov - nové diagnostické a prognostické biomarkery srdcového zlyhávania
Program: VEGA
Project leader: RNDr. Barteková Monika PhD.
Duration: 1.1.2014 - 31.12.2017

Molecular mechanisms involved in the effects of doxorubicin in rats with developed hypertension and ways of modulation of of these effects of doxorubicin by quercetin.
Molekulárne mechanizmy zahrnuté v účinkoch doxorubicínu u zvierat s rozvinutou hypertenziou a možnosti ovplyvnenia účinkov doxorubicínu pôsobením kvercetínu.
Program: VEGA
Project leader: RNDr. Barančík Miroslav DrSc.
Duration: 1.1.2015 - 31.12.2017

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Možná duálna funkcia P-glykoproteínu pri viacliekovej rezistencii leukemických buniek: efluxná pumpa a regulačný proteín.
Program: APVV
Project leader: RNDr. Barančík Miroslav DrSc.
Duration: 1.7.2014 - 30.6.2018

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Nové molekulárne mechanizmy poškodenia kardiovaskulárneho systému ionizujúcim žiarením a možnosti jeho cielenej medikamentóznej prevencie.
Program: VEGA
Project leader: D.h.c.,Prof., MUDr. Slezák Ján DrSc., FIACS
Duration: 1.1.2015 - 31.12.2017

Protection of mechanisms modulating endothelial permeability in the heart.
Ochrana mechanizmov modulujúcich permeabilitu endotelu v srdci.
Program: VEGA
Project leader: RNDr. Okruhlicová Ľudmila CSc.
Duration: 1.1.2016 - 31.12.2019

Protection of the heart from maladaptive extracellular matrix remodeling and searching the mechanisms of its regression.
Ochrana srdca pred maladaptívnou remodeláciou extracelularnej matrix a skúmanie mechanizmov jej regresie.
Program: VEGA
Project leader: RNDr. Szeiffová Bačová Barbara PhD.
Annotation:Heart diseases are accompanied by exracellular matrix remodeling and fibrosis resulting in development of heart failure and malignant arrhythmias. Fibrosis is a major medical problem without existing cure. However, there are cardioprotective compounds that exhibit antifibrotic effects but underlying mechanisms are poorly understood. This project is aimed to characterize key factors implicated in profibrotic signaling in rats suffering from hypertension, diabetes, hypothyroidism and post-infarction injury and to determine targets of examined pharmacological and nonpharmacological compounds. This approach should reveal signaling pathways and factors, whose modulation could hamper or reverse fibrosis. It is expected that findings of this preclinical study may outline design of clinical trials how to protect the heart from its dysfunction by non-invasive way.
Duration: 1.1.2015 - 31.12.2018

SCAVRAD - PROTECTION OF THE HEART IN SITUATIONS OF INCREASED PRODUCTION OF OXYGEN FREE RADICALS: RADIATION AND REPERFUSION INJURY
OCHRANA SRDCA V SITUÁCIÁCH ZVÝŠENEJ PRODUKCIE VOĽNÝCH KYSLÍKOVÝCH RADIKÁLOV: RADIAČNÉ A REPERFÚZNE POŠKODENIE
Program: APVV
Project leader: D.h.c.,Prof., MUDr. Slezák Ján DrSc., FIACS
Annotation:According to statistics, cardiovascular and cancer are the main cause of more than 93% of the global morbidity and mortality. One of the most used methods to treat patients with cancer is radiotherapy, which uses ionizing radiation. Ionizing radiation damages the cancer cells, leading to their apoptosis and to potential patient recovery. However, during irradiation of cancer cells may also occur unintended exposure of surrounding healthy tissue, which in turn can cause serious health complications including radiation-induced heart disease. Ionising radiation acts directly on the DNA of cells, or indirectly through the formation of free radicals, which then damage the individual organelles of cells or DNA. Production of oxygen free radicals, which in addition have a signaling function, at higher concentrations have toxic effects on all parts of the heart and blood vessels, is a common denominator of both ionizing radiation and inflammation, as well as ischemic and reperfusion injury. Therefore, research in this field, and finding novel suitable materials which can positively influence the effects of over
Duration: 1.7.2016 - 30.6.2020

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Relevancia nekroptózy v odumieraní myokardiálneho tkaniva v dôsledku rôznych typov poškodenia: vplyv na excitačno-kontrakčné prepojenie.
Program: VEGA
Project leader: Ing. Ferko Miroslav PhD.
Duration: 1.1.2016 - 31.12.2019

Investigation of regulatory mechanisms of cardiac cell-cell communication for targeted protection from heart failure.
Skúmanie regulačných mechanizmov medzibunkovej komunikácie v srdci pre cielenú ochranu pred jeho funkčným zlyhaním.
Program: VEGA
Project leader: RNDr. Tribulová Narcisa DrSc.
Annotation:Cardiac cell-to-cell communication via gap junction connexin (Cx) channels is essential for synchronised heart function. While disorders in expression, distribution and phosphorylation of Cx in of both human and animal heart diseases promote occurrence of malignant arrhythmias and heart failure. We hypothesize that targeted modulation of Cx channel function by exogenous and endogenous compounds may be a promising approach to protect proper heart function. Aim of this project is to elucidate mechanisms implicated in regulation of Cx43-mediated cardiac cell-to-cell communication in healthy and diseased heart. Research findings should enhance knowledge of cardiologists in this field and challenge the realization of clinical trials supporting novel approaches in prevention and/or treatment of heart diseases to fight sudden cardiac death.
Duration: 1.1.2016 - 31.12.2019

Study of the clinically relevant forms of preconditioning as an alternative method of myocardial protection against acute ischemia in the organism challenged with civilization diseases
Štúdium klinicky využiteľných foriem preconditioningu ako alternatívnej metódy ochrany myokardu pred akútnou ischémiou v organizme zaťaženom civilizačnými ochoreniami
Program: VEGA
Project leader: MUDr. Ravingerová Táňa DrSc., FIACS
Annotation:Hypertension, metabolic disorders, sex and aging have a negative impact on the adaptive mechanisms of innate cardioprotection and alter heart survival upon acute ischemia/reperfusion (I/R). These comorbidities suppress the mechanisms of cell signaling involved in protective effects of ischemic preconditioning (PC) and accelerate necrotic and apoptotic processes during I/R, reduce energy production and contribute to enhanced arrhythmogenesis. The project is aimed to investigate the possiblities to restore adaptive potential in the pathologically altered myocardium including aged heart by means of modulation of the intensity and forms of adaptive stimuli. Effects of clinically relevant forms of PC: „remote“ PC of the heart induced by ischemia of the distant organ and its pharmacological simulations by drugs regulating energy metabolisms and involved in the mechanisms of PC, as well as their genomic and non-genomic effects including the impact on mitochondrial function and apoptotic cascade will be investigated
Duration: 1.1.2015 - 31.12.2017

The role of extracellular vesicles in inter-organ communication related to remote cardioprotection
Úloha extracelulárnych vezikúl v medziorgánovej komunikácii zahrnutej v kardioprotekcii na diaľku (remote conditioning).
Program: VEGA
Project leader: RNDr. Barteková Monika PhD.
Annotation:Inter-organ communication plays a crucial role in cardioprotection induced by an ischemic (or other) insult on remote organ to the heart, called remote ischemic preconditioning, or remote conditioning in general. Extracellular vesicles (EVs) are membrane-bound structures secreted by a wide range of mammalian cell types that can be secreted and specifically taken up by other cells. Since EVs contain a high concentration of RNAs and proteins, they are of a high interest as potential mediators of remote cardioprotection, and thus for inter-organ signal transfer mechanisms in general. Revealing the role of EVs in communication between different cells and organs as well as identifying substances transported by EVs to be potential mediators of cardioprotection as the main goal of the current project could lead to better understanding of remote cardioprotection and inter-organ communication in general, and rise up new potential targets of therapy of heart ischemia.
Duration: 1.1.2016 - 31.12.2019

Projects total: 19