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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 - 31.12.2018

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


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

DYSRPONEP - Dynamics of myocardial damage: a role of necroptotic cell death and survival of cardiomyocytes.
Dynamika srdcového poškodenia: úloha nekroptotickej bunkovej smrti a prežívania kardiomyocytov.
Program: APVV
Project leader: MUDr. Ravingerová Táňa DrSc., FIACS
Annotation:Cardiomyocytes have a limited capability to proliferate, self-renew and repair. Therefore, the number of cardiac cells during postnatal development determines how the heart can deal with stress and workload demands. Both sudden acute or chronic progressive loss of heart cells are involved in the development of ventricular dysfunction and the progression of heart failure (HF). In cardiomyocyte loss, apoptosis seems to play a minor role compared to necrosis. In line with this, we have found that markers of a newly described form of regulated necrosis – necroptosis are increased in human failing hearts whereas apoptotic ones are unchanged. Although it has been proposed that these markers form a cytotoxic complex, it is unclear how it induces necroptotic cell death. In this process, a protein RIP1 plays an important role. However, when it is polyubiquitinated it may trigger pro-survival pathways instead. Stimuli, which preferentially trigger RIP1-mediated cell survival at the expense of cell death, are mostly unknown. In this project, we will study the cytotoxic action of necroptotic complexes with respect to translocation into cell structures, disturbed ion homeostasis and oxidative stress. In addition, we will study whichRIP1-associated signaling is triggered during cell survival (eg. ischemic preconditioning - IPC) and which RIP1 pathways lead to the contrary, death of cardiac cells in acute myocardial infarction and during the development of HF of various origin. By using a necroptosis inhibitor, we will try to determine whether it affects IPC-induced cardioprotection with respect to cell viability and whether its time-dependent application can relieve remodeling and cardiac dysfunction due to myocardial infarction or induce regression of damage. Cardiomoycytes, isolated hearts and in vivo studies will be used to investigate signaling pathways and autocrine/paracrine and systemwide responses to a primary impulz that induces the damage/ adaptation of the heart.
Duration: 1.7.2016 - 30.6.2020

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
Duration: 1.1.2017 - 31.12.2019

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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

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

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

Properties of the Na,K-ATPase, representing one of the crucial systems in maintaining the sodium homeostasis in the organism, after irradiation.
Vlastnosti Na,K-ATPázy, jedného z kľúčových systémov pre udržiavanie koncentrácie sodíka v organizme, v podmienkach zaťaženia organizmu po ožiarení.
Program: VEGA
Project leader: RNDr. Vrbjar Norbert CSc.
Annotation:The present project is oriented to obtain new data concerning the maintenance of intracellular homeostasis of sodium, representing one of the unavoidable factors for appropriate regulation of cellular viability, after application of radiotherapy. Using in vivo model (rat) we will investigate the influence of gamma irradiation on the cerebral and renal Na,K-ATPase which is one of the crucial systems in maintaining appropriate intracellular concentration of sodium ions. The data will contribute to elucidation of molecular background of processes involved in maintaining the cell’s viability in kidney and in brain from the aspect of possible protection of the organism against deleterious side-effects of radiotherapy.
Duration: 1.1.2017 - 31.12.2020

RIDD - Research of magnetic forms of iron in development of cardiovascular diseases and behavioural disorders
Výskum magnetických foriem železa v rozvoji kardiovaskulárnych chorôb a porúch správania
Program: APVV
Project leader: MUDr. Ravingerová Táňa DrSc., FIACS
Annotation:This project proposal is focused on the investigation of the role of iron in development of cardiovascular and behavioural disorders, prevalence of which is increasing during aging. The aim of this project is to investigate the impact of aging on the metabolism of biogenic iron and its magnetic properties in association with metabolic and functional alterations in the cardiovascular system and brain in rats with various genetic predispositions to hypertension. We will determine the molecular biological changes on the level of gene expression, their encoded proteins and the activities of the enzymes involved in the endogenous antioxidant protection, the regulation of nitric oxide production and cell death due to ferroptosis in course of aging. We will also investigate the impact of exogenously administered iron in the form of the biocompatible ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) on blood pressure regulation and function of the heart and blood vessels in conditions of normotension, chronically increased blood pressure and acute stress (i.e. acutely elevated blood pressure). Results achieved in this project will contribute to better understanding of the effects of the altered iron metabolism, magnetic forms of bodily iron, as well as iron in the form of USPIONs, on the cardiovascular and central nervous systems and to prevention of cardiovascular risk resulting from the use of USPIONs in targeted drug delivery or as the contrast materials for new imaging methods in medicine.
Duration: 1.7.2017 - 30.6.2021

Projects total: 14