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Mechanism of hypertrophic cardiomyopathy
Hadravová, Kateřina ; Horníková, Daniela (advisor) ; Benák, Daniel (referee)
Cardiomyopathies are a group of chronic cardiac diseases of unclear etiology. We can separate them by morphological and functional signs into restrictive, dilated and hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy is a relatively common disease in which the development of cardiac hypertrophy is not based on risk factors such as hypertension or atherosclerosis. Compared to acquired cardiac hypertrophy the hypertrophic cardiomyopathy is mainly caused by hereditary mutations. These mutations are mostly in genes for myosin heavy chain β and myosin binding protein C. Cardiac hypertrophy also presents with changes in the extracellular matrix caused by matrix metaloproteinases. They have a big impact on the morphology of cardiomyocytes and their loss, which in turn cause hypertrophy or left ventricle dilation. From medical point of view emphasis is put on prevention and early diagnosis using blood biomarkers. Among singnificant biomarkers are micro-RNAses, vascular endothelial growth factor B, NAD - dependent deacetylase sirtuin-3, growth/differentiation factor 15, glycoprotein 130 and calmodulin - dependent proteinkinase II. Causal treatment doesn't unfortunately exist, therefore symptomatic treatment is deployed using β blockers and calcium channel blockers. Newly used drugs include an...
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Potential physiological significance of thermal preconditioning
Ptáková, Alexandra ; Novotný, Jiří (advisor) ; Benák, Daniel (referee)
Short-term exposure of cells or whole body to mild hyperthermia, known as thermal pre- conditioning, is an experimental method used to provide cytoprotection against subsequent, otherwise harmful or even lethal, stress conditions. Thermal preconditioning is relatively easily feasible and could be used to prevent various health problems. The aim of this thesis is to sum- marize current knowledge about the impact of thermal preconditioning on cells and the whole organism. The possibilities of how to perform this method effectively are described here, toge- ther with the molecular mechanisms involved in the induction of cytoprotection. Some areas where thermal preconditioning could be used are also mentioned. Key words: thermal preconditioning, hyperthermia, cytoprotection, HSP, ischemia-reper- fusion injury
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The role of antioxidant system in cardioprotective models
Galatík, František ; Žurmanová, Jitka (advisor) ; Benák, Daniel (referee)
Ischemia/reperfusion injury is the main cause of death in patients suffering from cardiovascular disease. The efforts of tackling this problem have lead to the discovery of cardioprotective adaptations and subsequently - of several cardioprotective models. One of the mechanisms of the adaptations is the stimulation of antioxidant system as a protection against reactive oxygen species formed during reperfusion phase of ischemia/reperfusion. The aim of this thesis is to review the current knowledge regarding the role of antioxidant system in cardioprotective models and comparing them by this property. Key-words: cardioprotective models, antioxidant system, heart
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The role of demethylase FTO and adipokines in the heart: effect of chronic hypoxia
Benák, Daniel ; Hlaváčková, Markéta (advisor) ; Bardová, Kristina (referee)
Adaptace na chronickou hypoxii zvyšuje toleranci srdce k ischemicko-reperfuznímu poškození. Tato adaptace je umožněna řadou fyziologických změn na buněčné úrovni. Jednou z nich je změna v buněčném energetickém metabolismu. Tento proces může být regulován proteinem FTO (z angl. fat mass and obesity associated), demetylázou epigeneticky regulující buněčnou syntézu proteinů. Srdeční metabolismus může být také modulován adipokiny leptinem a adiponektinem. Cílem tohoto projektu bylo proto studovat roli FTO a adipokinů v chronicky hypoxickém srdci. Dospělí samci potkanů kmene Sprague Dawley byli adaptováni na dva modely kontinuální normobarické hypoxie (CNH; 12 % O2 a 10 % O2; 3 týdny). CNH (10 % O2) redukovala u těchto zvířat rozsah infarktu myokardu o 20 %. CNH (12 % O2) nebyla kardioprotektivní. Hladina proteinu FTO byla měřena v tkáni levých (LV) a pravých (RV) komor, stejně jako v játrech a koncovém mozku hypoxických i normoxických zvířat. Za normoxie je hladina FTO v RV o 50 % vyšší než v LV. Ve vysoce metabolicky aktivních tkáních jater a koncového mozku jsou pak hladiny FTO vyšší dokonce 6krát a 11krát. CNH (12 % O2) vedla k signifikantnímu nárůstu hladiny proteinu FTO v srdci. Jednalo se o 21% nárůst v LV a 27% v RV. Hladiny v játrech a koncových mozcích nebyly CNH ovlivněny. Silnější CNH (10 % O2)...
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The role of pro- and anti-inflammatory factors in adaptation of heart to hypoxia
Benák, Daniel ; Hlaváčková, Markéta (advisor) ; Holzerová, Kristýna (referee)
Myocardial hypoxia induces several physiological changes on cellular and molecular level in order to keep homeostasis in low oxygen conditions. Essential role in this adaptive response is played by secretory regulatory proteins called cytokines. Differences in concentrations of pro-inflammatory and anti-inflammatory cytokines during hypoxic conditions in the myocardium may significantly influence the fate of the heart tissue, i.e. contribute to its injury or protection. This knowledge is used in experimental cardioprotective strategies - adaptation to chronic hypoxia, ischemic preconditioning, postconditioning and remote conditioning - all of which affect the cytokine levels. The main pro-inflammatory cytokines are TNF-α, IL-1 and cytokine family IL-6. The principal anti-inflammatory cytokine is IL-10. This thesis aims to summarize the effects of pro- and anti-inflammatory cytokines in adaptation of heart to hypoxia and to cover their pathological and protective impact on the myocardium.
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