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Mechanism of cardioprotection elicited by cold acclimation
Csomová, Martina ; Žurmanová, Jitka (advisor) ; Holzerová, Kristýna (referee)
Myocardial infarction is the most common cause of death and disability worldwide. The term myocardial infarction refers to the death of cardiac cells, cardiomyocytes, caused by ischaemia resulting from a perfusion imbalance between the supply and demand for oxygen and nutrients. Recently, cold acclimatization has been found to reduce infarct size after ischemia/reperfusion (I/R) injury, but the mechanism is not fully clarified. Cold acclimatization elicits a thermoregulatory response by activating nontalamic thymogenesis associated with brown adipose tissue (BAT) activation. Cold-stimulated adrenergic signaling increases the expression of mitochondrial uncoupling protein 1 (UCP1), a key factor for heat production. Activated BAT increases metabolic turnover and thus likely contributes to the protection of the heart from myocardial infarction. In this work, I simulate I/R injury by establishing a hypoxic- reoxygenation (H/R) protocol in isolated adult cardiomyocytes. The aim of this work was to introduce different approaches to assess the viability of isolated cardiomyocytes and compare their utility, to investigate the effect of different cold adaptations on cardiomyocyte viability during the H/R protocol using the Cytation 5 multidetector, and subsequently to determine the effect of inhibitors of...
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Hif1a role in cardiovascular function and heart disease
Matějková, Kateřina ; Pavlínková, Gabriela (advisor) ; Holzerová, Kristýna (referee)
Hypoxia inducible factor 1 alpha (HIF1A) is a transcriptional factor, which plays a central role in the maintenance of homeostasis under hypoxic conditions. It regulates a wide variety of genes encoding proteins that influence metabolism, extracellular matrix composition, oxidoreductase activity or angiogenesis in response to reduced oxygen levels. When HIF1A protein function is impaired, the organism is unable respond appropriately to hypoxia. Altered HIF1A regulation can result in severe tissue damage and eventually lead to death. The heart, as an organ with a huge oxygen consumption, is susceptible to various pathologies caused by hypoxic stress. The role of HIF1A in the heart is rather ambiguous and remains to be elucidated. It plays a role in cardioprotective mechanisms but also promotes the development of inflammation and apoptosis. This thesis aims to clarify the role of HIF1A in maintaining physiological functions of the heart during adaptation to hypoxic conditions using a mouse model with heterozygous Hif1a+/- deletion. Experiments involving molecular and cell biology methods performed on left ventricular tissue were preceded by bioinformatic analysis of data obtained by RNA sequencing of isolated cardiomyocytes. RNA sequencing data were analyzed using the R scripting language (packages...
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The role of batokines in cardioprotection elicited by mild cold acclimation
Zvolská, Veronika ; Žurmanová, Jitka (advisor) ; Holzerová, Kristýna (referee)
Myocardial infarction remains one of the most serious diseases of civilization worldwide. The aim of the research is therefore to search for new strategies to protect the heart from ischemia-reperfusion (I/R) damage and its consequences. New findings can be used in clinical practice and for the prevention and treatment of heart diseases. This work builds on a study from our laboratory that developed a model of mild cold acclimation (5 weeks, 8 řC) associated with a significant reduction in infarct size after rat myocardial I/R without side effects. However, further study is needed to elucidate the mechanism of the cardioprotective effect. The diploma thesis was focused on the potential influence of known batokines, fibroblast growth factor (FGF21) and interleukin 6 (IL-6). Furthermore, we aimed to introduce a method for isolating adult rat cardiomyocytes and a procedure for verifying the viability and resistance of myocardial cells under the load of hypoxia and oxidative stress at the workplace. Effective cardioprotection of the mild cold acclimation was confirmed in the work. Acute ablation of BAT before the ischemia-reperfusion protocol had no effect on infarct size. The cardiomyocyte isolation method was successfully introduced and the protective effect of acute cold (10 days, 8 řC) was...
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Role of antioxidant enzymes in cardioprotective regimens of cold acclimation
Špínová, Šárka ; Žurmanová, Jitka (advisor) ; Holzerová, Kristýna (referee)
The effect of cold on the organism depends on the degree of cold and its duration. Cold acclimation induces a thermoregulatory response, shivering thermogenesis and subsequently the development of non-shivering thermogenesis associated with the activation of brown adipose tissue. Exposure to mild cold in the form of hardening possesses beneficial effects on the whole organism and recently the cardioprotective effects of mild cold acclimation has been described. Increased antioxidant capacity has been demonstrated in the mechanism of cardioprotection induced by hypoxia. The aim of this thesis was to find out whether the protective effect of mild cold acclimatization (8 ± 1 řC) is associated with a change in the capacity of the antioxidant system. To achieve this goal, the protein levels of the main antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, thioredoxin, thioredoxin reductase, aconitase, heme oxygenase) were determined during acclimation to mild cold, specifically in 1-3-10 days and subsequently after 5 weeks, and after a 2-week recovery. The results showed changes in most of the antioxidant proteins, however the effect on cold-elicited cardioprotection must be further verified. Key words: heart, cold acclimation, superoxide dismutase, catalase, glutathione...
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Supercomplexes in the respiratory chain of mitochondria
Mikulová, Tereza ; Houštěk, Josef (advisor) ; Holzerová, Kristýna (referee)
Mitochondria are very important organelles of eukaryotic cell. In mitochondria, there are located many metabolic reactions including oxidative phosphorylation (OXPHOS). In this process, respiratory chain enzyme complexes couple the oxidation of NADH and FADH2 to vectorial proton transport across the inner mitochondrial membrane. ATP synthase then uses the resulting electrochemical potential to synthesize ATP from ADP and phosphate. Recent studies of the OXPHOS demonstrate higher structures of complexes so-called supercomplexes which facilitate substrate channeling. Formation of supercomplexes plays a role in the assembly and stability of the complexes, suggesting that the supercomplexes are the functional state of the respiratory chain.
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The effect of season on mitochondrial swelling of rat heart after cold acclimation
Kašík, Petr ; Horníková, Daniela (advisor) ; Holzerová, Kristýna (referee)
Risk of death from cardiovascular disease is substantially increased throughout winter season and by exposure of organism to acute cold stress. However, several studies have suggested that some cold acclimation models could act cardioprotectively. The thesis is focused on effects of acute and chronic cold acclimation on swelling of rat heart mitochondria. Mitochondrial swelling is, besides other things, caused by massive influx of Ca2+ into the mitochondria especially during ischemia-reperfusion injury. By that, mitochondria permeability transition pore is being opened and subsequently, this could end up in mitochondrial burst and cell death, eventually. Lower rate of mitochondrial swelling indicates greater mitochondrial resistance. The results express higher mitochondrial resistance after acute cold exposure and chronic cold acclimation. Key words: cold, mitochondria, Ca2+ ions, swelling, MPTP, myocardium, ROS, ischemia
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Application of nanofiber scaffolds for vesel regeneration
Bezděková, Dagmar ; Amler, Evžen (advisor) ; Holzerová, Kristýna (referee)
Although plenty of systems for vessel regeneration have been developed, no system is successful in small diameter (under 6 mm) vessel replacement yet. Synthetic materials, such as Dacron and ePTFE, have good results in large vessels replacement, but they cause thrombosis in small vessels. In addition, they are not degradable and do not allow a natural remodeling of the vessel system. Furthemore, endothelial cells, which are essential for creating natural antithrombogenic endothelium, do not adhere on these materials, as well as smooth muscle cells. Decellularized xenogenic material is the non-synthetic alternative for vessel regeneration. Appropriate detergent removes donor's cells and only extracellular matrix remains, which is able to host acceptor's cells. The main disadvantages of this system are difficulties with animal's nurture and structure violations after detergent is used. It appears that electrospun materials are the best alternative. The relatively simple process can be modified in many ways and provides then a scaffold, which mimics extracellular matrix. A big advantage of this process is the possibility to incorporate bioactive substances into a fiber. The substances serve there as an attractant for blood cells or as an anticoagulation factor. In combination with the progenitor cells seems...
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The role of Arachidonic acid metabolites in cardiovascular system and signaling of heart failure
Liptáková, Andrea ; Žurmanová, Jitka (advisor) ; Holzerová, Kristýna (referee)
Arachidonic acid (AA) is polyunsaturated acid that plays an important role in regulation of physiology, bioenergetic and signalling cascades in the heart. AA released by phospholipase A2-catalysed hydrolysis of membrane phospholipids serves as substrate for cyclooxygenase, lipooxygenase and cytochrome P450 epoxygenase to produce a wide spectrum of lipid second messengers, eicosanoids. These very biologically potent molecules regulate a number of cellular processes in the cardiovascular system and changes in their composition and concentration significantly contribute to heart failure. The aim of this thesis was to summarize current knowledge about the role of AA in failing heart. Keywords : Heart, Arachidonic Acid, Heart Failure, Eicosanoids, Cardiovascular System
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The role of protein kinase C and its targets in cardioprotection
Holzerová, Kristýna ; Hlaváčková, Markéta (advisor) ; Alán, Lukáš (referee) ; Vízek, Martin (referee)
The mortality of cardiovascular diseases remains high and it likely tends to increase in the future. Although many ways how to increase the resistance against myocardial ischemia- reperfusion damage have been described, few of them were transferred into clinical practice. Cardioprotective effect of chronic hypoxia has been described during 60s of the last century. Its detailed mechanism has not been elucidated, but a number of components has been identified. One of these components presents protein kinase C (PKC). The role of PKC was described in detail in the mechanism of ischemic preconditioning, but its involvement in the mechanism of cardioprotection induced by chronic hypoxia remains unclear. One reason is the amount of PKC isoforms, which have often contradictory effects, and the diversity of hypoxic models used. The most frequently mentioned isoforms in connection with cardioprotection are PKCδ and PKCε. The aim of my thesis was to analyze changes in these PKC isoforms at two different cardioprotective models of hypoxia - intermittent hypobaric (IHH) and continuous normobaric hypoxia (CNH). We also examined the target proteins of PKCδ and PKCε after the adaptation to IHH, which could be involved in the mechanism of cardioprotection. These included proteins associated with apoptosis and...
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