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The role of Akt kinase in cardioprotective mechanisms induced by chronic hypoxia
Grešíková, Milada ; Žurmanová, Jitka (advisor) ; Svatoňová, Anna (referee)
Cardiovascular diseases (CVDs) are the most widely spread diseases of modern civilization. Mechanisms involved in the protection of myocardial tissue are for that very reason in the focus of cardiovascular research. The adaptation to chronic hypoxia has been studied for many years in the context of its positive effects on heart function and its increased tolerance to ischemia-reperfusion (I/R) injury. This Master thesis describes the role of Akt kinase in the mechanisms leading to myocardial protection against I/R injury using the model of adaptation to chronic normobaric hypoxia (CNH). The hearts from male Wistar rats, that were kept in normoxic or hypoxic conditions (O2 0.1) for the period of 3 weeks, were retrogradely perfused by oxygenated Krebs-Henseleit solution and then subjected to 10 min of ischemia and 10 min of reperfusion. Samples prepared from left ventricles (LV) of experimental hearts were later used for protein analyses. The adaptation to CNH leads to increased phosphorylation of Akt kinase on Ser473, but it did not affect the phosphorylation on Thr308 nor the total protein level of Akt. A significant increase in Bcl-2/Bax ratio was also observed in hearts adapted to CNH. This Master thesis further elucidates, how Akt signaling pathway and its activation are affected by short...
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Cardiac ischemic tolerance in rats subjected to adaptation to chronic hypoxia and physical exercise: the role of TNF-alpha.
Svatoňová, Anna
Cardiovascular diseases represent the most important health risk factors because they are responsible for more than 50% of total mortality. Among them, the ischemic heart disease is leading cause of mortality. From the whole spectrum of different cardioprotective phenomena we have selected: 1) adaptation to chronic normobaric hypoxia (CNH) as the traditional experimental model in our laboratory area and 2) protective effect of exercise which in recent years represents promising and clinically relevant protective mechanism. The whole thesis is based on two studies. Aim of the first study was to characterize the expression of the main pro-inflammatory cytokine, TNF-α, in hearts of rats adapted to CNH. Chronic TNF-α inhibition by infliximab was used for discovering of certain role of TNF-α in CNH. We showed that increased myocardial level of TNF-α during adaptation to CNH was contributed via its receptor TNFR2 and nuclear factor κB-dependent activation of protective redox signalling with increased antioxidant defence. This adaptive pathway participates on the infarct size-limiting effect of CNH. Aim of the second study was find out whether exercise training and CNH could play synergy in cardiac protection in rats model. We reported that CNH and exercise reduced infarct size but their combination...
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Cardiac ischemic tolerance in rats subjected to adaptation to chronic hypoxia and physical exercise: the role of TNF-alpha.
Svatoňová, Anna ; Neckář, Jan (advisor) ; Maxová, Hana (referee) ; Szárszoi, Ondrej (referee)
Cardiovascular diseases represent the most important health risk factors because they are responsible for more than 50% of total mortality. Among them, the ischemic heart disease is leading cause of mortality. From the whole spectrum of different cardioprotective phenomena we have selected: 1) adaptation to chronic normobaric hypoxia (CNH) as the traditional experimental model in our laboratory area and 2) protective effect of exercise which in recent years represents promising and clinically relevant protective mechanism. The whole thesis is based on two studies. Aim of the first study was to characterize the expression of the main pro-inflammatory cytokine, TNF-α, in hearts of rats adapted to CNH. Chronic TNF-α inhibition by infliximab was used for discovering of certain role of TNF-α in CNH. We showed that increased myocardial level of TNF-α during adaptation to CNH was contributed via its receptor TNFR2 and nuclear factor κB-dependent activation of protective redox signalling with increased antioxidant defence. This adaptive pathway participates on the infarct size-limiting effect of CNH. Aim of the second study was find out whether exercise training and CNH could play synergy in cardiac protection in rats model. We reported that CNH and exercise reduced infarct size but their combination...
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The role of Akt kinase in cardioprotective mechanisms induced by chronic hypoxia
Grešíková, Milada ; Žurmanová, Jitka (advisor) ; Svatoňová, Anna (referee)
Cardiovascular diseases (CVDs) are the most widely spread diseases of modern civilization. Mechanisms involved in the protection of myocardial tissue are for that very reason in the focus of cardiovascular research. The adaptation to chronic hypoxia has been studied for many years in the context of its positive effects on heart function and its increased tolerance to ischemia-reperfusion (I/R) injury. This Master thesis describes the role of Akt kinase in the mechanisms leading to myocardial protection against I/R injury using the model of adaptation to chronic normobaric hypoxia (CNH). The hearts from male Wistar rats, that were kept in normoxic or hypoxic conditions (O2 0.1) for the period of 3 weeks, were retrogradely perfused by oxygenated Krebs-Henseleit solution and then subjected to 10 min of ischemia and 10 min of reperfusion. Samples prepared from left ventricles (LV) of experimental hearts were later used for protein analyses. The adaptation to CNH leads to increased phosphorylation of Akt kinase on Ser473, but it did not affect the phosphorylation on Thr308 nor the total protein level of Akt. A significant increase in Bcl-2/Bax ratio was also observed in hearts adapted to CNH. This Master thesis further elucidates, how Akt signaling pathway and its activation are affected by short...
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Cardiac ischemic tolerance in rats subjected to adaptation to chronic hypoxia and physical exercise: the role of TNF-alpha.
Svatoňová, Anna
Cardiovascular diseases represent the most important health risk factors because they are responsible for more than 50% of total mortality. Among them, the ischemic heart disease is leading cause of mortality. From the whole spectrum of different cardioprotective phenomena we have selected: 1) adaptation to chronic normobaric hypoxia (CNH) as the traditional experimental model in our laboratory area and 2) protective effect of exercise which in recent years represents promising and clinically relevant protective mechanism. The whole thesis is based on two studies. Aim of the first study was to characterize the expression of the main pro-inflammatory cytokine, TNF-α, in hearts of rats adapted to CNH. Chronic TNF-α inhibition by infliximab was used for discovering of certain role of TNF-α in CNH. We showed that increased myocardial level of TNF-α during adaptation to CNH was contributed via its receptor TNFR2 and nuclear factor κB-dependent activation of protective redox signalling with increased antioxidant defence. This adaptive pathway participates on the infarct size-limiting effect of CNH. Aim of the second study was find out whether exercise training and CNH could play synergy in cardiac protection in rats model. We reported that CNH and exercise reduced infarct size but their combination...
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The adenylyl cyclase signaling system in normal and failing myocardium
Karlovská, Ivana ; Novotný, Jiří (advisor) ; Svatoňová, Anna (referee)
This bachelor thesis describes a signal pathway of adenylyl cyclase, which plays a key role in the modulation of heart rate and force of contraction. This pathway begins with membrane-bound β- adrenergic receptors that activate the enzyme adenylyl cyclase. Adenylyl cyclase produces second messengers by reverting ATP to cAMP. Several changes occur in this pathway in failing heart. The most striking changes occur in β-adrenergic receptors, but there are some changes on the level of adenylyl cyclase and G proteins as well. Most of these changes are related to chronic high levels of catecholamines, especially norepinephrine. Some medications try to reverse these adverse effects of norepinephrine. β-blockers are traditional drugs for treating heart failure. However, adenylyl cyclase may be also considered as potential target for pharmacotherapeutic interventions in the future. Powered by TCPDF (www.tcpdf.org)
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