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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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The role of protein kinase C in cardioprotection elicited by mild cold acclimation
Lážnovská, Lucie ; Žurmanová, Jitka (advisor) ; Hlaváčková, Markéta (referee)
This master's thesis examines the role of protein kinase C (PKC) in cardioprotection induced by mild cold. PKC is a crucial signaling transduction enzyme that regulates cell growth, differentiation, and survival of the cell. Mild cold, as a novel potential therapeutic strategy, protects tissues from ischemic damage. Studies by Yang et al. suggest that hypothermia activates PKC in cardiomyocytes, triggering a cascade of signaling pathways with protective effects. PKC phosphorylates and activates proteins crucial for cell survival and recovery after ischemia, while also inhibiting apoptosis and limiting the formation of reactive oxygen species that contribute to cell damage during ischemia and reperfusion injury. This work focuses on understanding the molecular mechanisms and signaling pathways associated with the role of PKCε and δ isoforms in cardioprotection induced by mild cold, which could contribute to the development of new therapeutic strategies protecting the heart from ischemic damage. Keywords: protein kinase C, PKCε, PKCδ, mild cold, cardioprotection
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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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The role of uncoupling proteins (UCP) in cardioprotection
Furmánková, Tereza ; Horníková, Daniela (advisor) ; Adamcová, Kateřina (referee)
Cardiovascular disease (CVD) is the world's leading cause of death. Almost 18 million people die of CVD each year, and the prevalence continues to rise for both men and women. It is now clear that the maintenance of mitochondrial membrane potential can play an important role in the pathophysiology of the heart and it is involved in cardioprotective mechanisms. Mitochondrial membrane potential can be affected in a various of ways, one of them is the stimulation of uncoupling proteins. An elaboration of previous findings in this work has shown that uncoupling proteins have the effect of reducing oxygen radicals, inhibiting apoptosis, affect the production of ATP and atherosclerotic plaques and protect the heart from lipid toxicity. There are several ways to regulate their gene expression, and influencing these pathways may be a way to achieve cardioprotection. Key words: uncoupling proteins, mitochondria, cardioprtoection, thyroid hormones, fatty acids, adipose tissue, reactive oxygen species, FGF21
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The role of PGC1 in cardioprotective mechanisms
Jeřábková, Adéla ; Horníková, Daniela (advisor) ; Kolář, David (referee)
One of the leading causes of death worldwide is cardiovascular diseases. Researchers are, therefore, dealing with the mechanisms that induce a cardioprotection. Cardioprotection is a general pathophysiological term under which we understand myocytes protection against damage by ischemia and subsequent reperfusion impairment, inflammation, hypertension, and toxic and degenerative changes, including some types of apoptosis. One of the less common ways of cardioprotection is a cold adaptation. Adaptive thermogenesis is an important part of energy homeostasis and protection against obesity, metabolic disorder threatening heart. The PGC family of proteins plays a very important role in adaptive thermogenesis. This thesis summarizes the current state of literature in cold adaptation issues, especially the role of PGC1α and its effects at the cellular and tissue level. mRNA expression of PGC-1α is strongly induced in brown fat and skeletal muscles of mice exposed to cold. PGC-1α also increases the transcriptional activity of PPAR-γ and thyroid hormone receptor protein on UCP-1 (uncoupling protein). UCPs (uncoupling proteins) are small proteins localized to the inner side of the mitochondrial membrane to facilitate the transport of protons, which they release into concentration gradient without ATP...
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Autophagy in the heart
Šprláková, Katarína ; Hlaváčková, Markéta (advisor) ; Tomšů, Eva (referee)
Currently, it is growing evidence that autophagy is involved in the prevention of various diseases, which of course also includes heart diseases. This thesis is therefore aimed at clarifying the role of autophagy in the heart, especially during ischemia and subsequent reperfusion. Autophagy is a physiological cellular process by which the cell maintains homeostasis by eliminating long-lived proteins and damaged organelles. The role of autophagy during ischemia/reperfusion in the heart is complex. Predominantly it functions as a pro-survival pathway, because it protects the heart from ischemia or hypoxia. However, when triggered over, which happens during reperfusion, it may lead to cell death. In the heart autophagy is activated in response to various stimuli, such as decrease in ATP and subsequent activation of AMPK, protein Bnip3, reactive oxygen and nitrogen species, the opening of mitochondrial permeability transition pore, endoplasmic reticulum stress or unfolded protein response.
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Cardiac ischemic tolerance of hypertensive rats
Jelínek, Jan ; Neckář, Jan (advisor) ; Sotáková, Dita (referee)
The aim of this thesis is to summarize current knowledge about the influence of the ischemic- reperfusion injury at the myocard of hypertensive subjects. First part of this thesis is focused on the description of ischemia, reperfusion and changes in the myocardial metabolism during these processes. These changes in the myocardial metabolism are for example necrosis or apoptosis of the myocardial cells. The second part describes the currently known cardioprotective phenomena. This part also compares their effects. The signalization of preconditioning, the second window of preconditioning and the postconditioning are described here in more details. Third part is focused on the description of the risk factors connected to the ICHS and hypertension. It describes also classes of hypertension, clinical and experimental methods of hypertension treatment, description of the laboratory breeds of hypertensive rats. In the last part of this thesis I describe the influence of hypertension on the I-R injury in current laboratory studies. In the most studies spontaneously hypertensive rats (SHR) were used. As a normotensive controls Wistar-Kyoto rats were mostly used. For some other experiments transgenic genetic rats (TGR) were used. Powered by TCPDF (www.tcpdf.org)
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Mitochondrial dynamics in myocardium.
Weissová, Romana ; Nováková, Olga (advisor) ; Kalous, Martin (referee)
The heart is an absolutely vital body organ, which requires sufficient amount of active mitochondria for its energy demanding activity. The functionality of a mitochondrial population is maintained through mitochondrial turnover, encompassing mitophagy removing damaged mitochondria and mitochondrial biogenesis responsible for the emergence of new organelles. Dynamic processes of mitochondrial fusion and fission can also contribute to the maintenance of a healthy mitochondrial population. Mitochondrial fusion and fission have not yet been proven in cardiomyocytes, although these cells possess all the proteins required for these events. These processes, however, take on the importance during pathological conditions, when changes in the amount of protein applied in the mitochondrial dynamics occur. The modification in mitochondrial phenotype leads to the cell damage. Understanding the role of mitochondrial dynamics in myocardium may contribute to the development of new heart diseases treatments.
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Role of protein kinase C isoforms in cardioprotective mechanism of chronic hypoxia
Hlaváčková, Markéta ; Novák, František (advisor) ; Kopecký, Jan (referee) ; Novotný, Jiří (referee)
Cardiovascular diseases, particularly acute myocardial infarction, are one of the leading causes of death in developed countries. It is well known that adaptation to chronic intermittent hypobaric hypoxia (IHH) confers long-lasting cardiac protection against acute ischemia/reperfusion injury. Protein kinase C (PKC) appears to play a role in its cardioprotective mechanism since the administration of general PKC inhibitor completely abolished the improvement of ischemic tolerance in IHH hearts. However, the involvement of individual PKC isoforms remains unclear. Therefore, the primary aim of this study was to investigate the potential involvement of PKCδ and PKCε, the most prevalent PKC isoforms in rat heart, in the mechanism of IHH-induced cardioprotection. We showed that IHH up- regulated PKCδ protein in left ventricle, enhanced its phosphorylation on Ser643 and increased its co-localization with markers of mitochondrial and sarcolemmal membranes. PKCδ subcellular redistribution induced by IHH as well as the infarct size-limiting effect of IHH was reversed by acute treatment with PKCδ inhibitor rottlerin. These data support the view that PKCδ plays a significant role in IHH-induced cardioprotection. On the other hand, adaptation to IHH decreased the PKCε total protein level without affecting its...
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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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