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The role of C-reactive protein in cardiac ischemic tolerance
Perglerová, Aneta ; Neckář, Jan (advisor) ; Vebr, Pavel (referee)
Ischemic heart disease (CHD) is a set of pathophysiological states, disorders of blood flow and oxygen supply of the myocardium due to vascular constriction or thrombus blockage. Inflammation plays an important role in CHD. The inflammatory response is associated with the synthesis of acute phase proteins in the liver such as C-reactive protein (CRP). CRP plays an important role in acute forms of CHD such as myocardial infarction (MI). The development of CHD may be supported by the occurrence of some of the risk factors (eg. atherosclerosis, hypertension, plasma CRP). Increased CRP levels may support the initiation of atherosclerotic plaque formation as well as in the case of hypertension the presence of CRP increases the risk of developing CHD. The healing proces after acute MI is accompanied by an inflammatory phase where CRP occurs naturally and CRP is important to accelerate inflammation. There may be a situation which inflammation goes into a chronic phase because it is not terminated in time, with constant CRP synthesis. High levels of CRP may decrease the prognosis after MI. The elevated plasma CRP has a negative effect on the expansion of MI and the associated ventricular dilatation, which may result in a rupture of the cardiac wall. Hypertrophy is the compensatory mechanism of the...
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The effect of maternal diabetes on embryonic cardiovascular development and fetal programing
Čerychová, Radka ; Pavlínková, Gabriela (advisor) ; Nováková, Olga (referee) ; Neckář, Jan (referee)
Maternal diabetes mellitus negatively affects embryonic development and increases the risk for congenital malformations. Besides direct teratogenicity, diabetic intrauterine milieu can predispose an individual to chronic diseases later in life, including cardiovascular diseases, obesity, and diabetes mellitus, in a process termed fetal programing. Molecular mechanisms of embryonic and fetal responses to maternal diabetes are still not fully elucidated. Using mouse model, we show that maternal diabetes induces gene expression changes in the hearts of developing embryos. The most significant changes in the expression of 11 selected genes were detected at the developmental stage associated with completion of cardiac septation, myocardial mass expansion, and increased insulin production in the embryonic pancreas. These affected genes encode products involved in the epithelial-to-mesenchymal transition, a crucial process in heart development. Using immunohistochemistry, we detected increased hypoxia in the diabetes-exposed hearts at the critical stage of cardiac development. Correspondingly to increased hypoxia, the expression of hypoxia-inducible factor 1α (HIF1α) and vascular endothelial growth factor A was increased in the heart of diabetes-exposed embryos. Based on our results indicating the...
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Opioid receptors and their signaling system in the myocardium
Ladislav, Marek ; Novotný, Jiří (advisor) ; Neckář, Jan (referee)
The main objective of this bachelor thesis is to systematically collect and sort information about opioid receptors and their signaling system in the myocardium. Heart activity is controlled mainly by adrenergic signaling, and this work therefore contains also some data concerning the characteristic and significance of other relevant receptors. For better understanding, general basic information about opioid system, especially about the receptors and their signaling, is also provided. Relatively little is known about opioid receptors in the myocardium even though these receptors may have an important role especially in various pathophysiological conditions. There can be several reasons for this. The possibility of further characterization of opioid receptors in the myocardium is rather difficult due to the relatively small number of these receptors in heart tissue. The situation is somewhat complicated also by some differences in the modulation of cardiac function among different species. The complete molecular mechanism by which opioid receptors act on the myocardium has not yet been fully uncovered. Especially in the case of humans this knowledge can be crucial, because these receptors and their ligands could be used for medical purposes.
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The role of the endothelin system in development of hypertension and hypertensive end-organ damage in Ren-2 transgenic rats
Opočenský, Martin ; Červenka, Luděk (advisor) ; Neckář, Jan (referee) ; Widimský, Jiří (referee)
The role of the endothelin system in development of hypertension and hypertensive end- organ damage in Ren-2 transgenic rats Endothelin-I (ET-I) has been described as one ofthe most powerful vasoconstrictors, that also play a role in the regulation of renal hemodynamics. ET system plays an important role in the pathogenesis of salt-sensitive models of hl'pertension. The benefícial effects of ET receptor blockers in modulating target-organ damage arise rrom their antiproliferative action. There is, however, a large discrepancy in the effect of ET between various models of hypertension. The hypertensive rat strain transgenic for the mouse Ren-2 (TGR) renin gene is a valuable monogenetic model of renin-dependent and thus angiotensin lI(Ang ll) - dependent hypertension, which exhibits typical signs of fulminant hypertension,i.e. reduced glomerular fíltration rate and proteinuria associated with g1omerulosderosis. Moreover, it carries a salt- sensitive component. We have recently found that nonselective endothelin ETA/ETB receptor blockade markedly improves survival rate and ameliorates end'-organ damage in malcTGR without lowering blood pressure. Because activation ofthe ETA receptor may be responsible for the detrimental effects of ET in the development of hypertension, our study was performed to...
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Reactivity of pulmonary vessels to hypoxia
Koubský, Karel ; Herget, Jan (advisor) ; Červenka, Luděk (referee) ; Neckář, Jan (referee)
Hypoxic pulmonary vasoconstriction (HPV) is a physiological mechanism that maintains optimal oxygenation of blood in the lungs. However, chronic hypoxia causes hypoxic pulmonary hypertension (HPH). Increased reactive oxygen species (ROS) participate in the pathogenesis of HPH. Oxidative stress can cause NO synthase uncoupling and subsequent production of superoxide instead of NO. Increase in intracellular Ca2+ concentration in pulmonary smooth muscle cells is required for pulmonary vasoconstriction. However, vessel tone can also be regulated by vascular smooth muscle cells' calcium sensitivity (without Ca2+ concentration changes). Increase of calcium sensitivity plays a role in HPV and HPH. This study focuses on three mechanisms to influence the increased calcium sensitivity in HPV a HPH: (1) Rho kinase inhibition, (2) effort to re-couple NO synthase, and (3) vasorelaxant effect of tyrosine kinase inhibitors. Normobaric hypoxic chamber (10% O2) or the combination of hypoxia and vascular endothelial growth factor receptor blockade was used to induce pulmonary hypertension in rats. (1) The effect of acute and chronic Rho kinase inhibition was studied on pressure-flow relationship (P/Q) in isolated perfused lungs. Acute Rho kinase inhibition decreased the basal tone of pulmonary vessels in HPH...
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Neural mechanisms in the pathogenesis of spontaneous hypertension in the rat
Vavřínová, Anna ; Zicha, Josef (advisor) ; Haluzík, Martin (referee) ; Neckář, Jan (referee)
Both sympathoneural and sympathoadrenal systems are involved in the regulation of arterial blood pressure and in the pathogenesis of hypertension. Spontaneously hypertensive rats (SHR), the mostly used animal model of genetic hypertension, is characterized by multiple molecular, morphological and functional alterations at different levels of sympathoneural and sympathoadrenal systems. The study of young prehypertensive SHR allows to reveal the abnormalities preceding hypertension development, whereas adult SHR with established hypertension offers a better model for the treatment of human essential hypertension. The aim of my PhD Thesis was to describe abnormalities in sympathoneural and sympathoadrenal systems in SHR under different conditions. Firstly, ontogenetic differences which might contribute to hypertension development were determined. Secondly, the effect of chemical sympathectomy induced by guanethidine in adulthood on cardiovascular parameters and on the compensatory mechanisms counteracting the reduction of blood pressure were studied. Thirdly, stress-induced cardiovascular response and stress-induced changes of sympathoneural and sympathoadrenal systems were described in adult SHR. My Thesis brought several important results. The increased adrenal catecholamine content and the...
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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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Myocardial tolerance to ischemia/reperfusion injury - possible protective mechanisms
Alánová, Petra ; Neckář, Jan (advisor) ; Nováková, Olga (referee) ; Vaněčková, Ivana (referee)
Ischemic heart disease is the leading cause of death and disability worldwide. The effects of ischemic heart disease are usually attributable to the detrimental effects of acute myocardial ischemia/reperfusion (I/R) injury. The aim of the thesis was to contribute to current effort to clarify the basis of mechanisms that could save the heart from I/R injury. The whole thesis is based on four studies; while the first three are published, the fourth one has been under revision. In the first study, we proved the involvement of nitric oxide (NO) in the cardioprotective mechanism of chronic hypoxia (CH). We described that exogenously increased availability of NO as well as inhibition of phosphodiesterase type 5 led to increased myocardial tolerance of normoxic and chronically hypoxic rats. The effects of both interventions were not additive, suggesting that NO is included in cardioprotective signaling of CH. Second study continued in investigating molecular mechanisms underlying cardioprotection induced by CH. We showed that infarct size-limiting effect of adaptation to CH was accompanied by increased myocardial concentration of tumor-necrosis factor alpha (TNF-α) and TNF-α receptor R2. In the third study, we examined the effect of dexrazoxane (DEX), the only clinically approved drug against...
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