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Myocardial phospholipases A2 and oxidative stress
Závišková, Kristýna ; Míčová, Petra (advisor) ; Chytilová, Anna (referee)
Heart and vascular diseases, in which oxidative stress plays an important role, are the most frequent cause of death in developed countries. Therefore today's researches focus on clarifying signaling pathway and their components that operates in these processes. One of the possible key factors can be phospholipases A2. These enzymes hydrolyze unsaturated fatty acids from C2 position on phospholipids, which easily subject to the oxidative modification due to their double bonds. There are five groups: the secreted, the cytosolic, the calcium independent, the platelet-activating factor acetylhydrolases and the lysosomal phospholipases A2. They differ in the requirement for calcium ions for its activity, molecular weight, position of disulfide bonds and amino acids sequences in the active site. Their main importance is to keep the stability and integrity of cell membranes and produce lipid signaling molecules (free fatty acids, lysophospholipids, eicosanoids). The phospholipases A2 play a dual role during oxidative stress in myocardium. First, they have a positive effect by protecting membranes against oxidative stress due to their higher affinity for removal of peroxidized fatty acids from membrane phospholipids. On the other hand, the phospholipases A2 can also cause destructive effects during...
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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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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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Relation between the reperfusion of pulmonary arteries after an acute pulmonary embolism to the development of chronic thromboembolic pulmonary hypertension.
Mrózek, Jan ; Jansa, Pavel (advisor) ; Maxová, Hana (referee) ; Hutyra, Martin (referee)
Relation between the reperfusion of pulmonary arteries after acute pulmonary embolism to the development of chronic thromboembolic pulmonary hypertension Incomplete resolution of thromboemboli following acute pulmonary embolism (PE) is a key factor in development of chronic thromboembolic pulmonary hypertension (CTEPH). In our study, we evaluated the incidence, risk factors and clinical impact of incomplete reperfusion after acute PE. Study population and methods: 85 patients after the first acute PE were assessed clinically and by pulmonary scintigraphy and echocardiography at month 6, 12 and 24 after an acute PE. Results: Incomplete reperfusion was detected in 23.5 % of patients after 6 months, in 24.9 % of patients after 12 months and in 18.6 % of patients after 24 months. At month 6, patients with incomplete reperfusion were more obese when compared with patients with normal reperfusion BMI 30.8 vs 28.3 kg/m2 ; p=0.012) and their initial hemoglobin levels were higher (143.0 vs 136.0 g/l; p=0.012). Similar results were observed at month 12 - patients with residual perfusion defects were more obese (BMI 31.1 vs 28.5; p=0.016) with higher initial hemoglobin levels (144.0 vs 136.0; p=0.007). Patients with incomplete reperfusion at month 24 were significantly older (67.7 vs 55.0 years; p=0.02), their...
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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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Reactive oxygen species and their role in myocard injury
Selingerová, Josefína ; Kalous, Martin (advisor) ; Rauchová, Hana (referee)
Cardiac tissue is very sensitive to oxygen deprivation. Ischemia and subsequent reperfusion are the source of metabolic and structural changes. They lead to irreversible tissue damage and cell death. Under this conditions the increased production of reactive oxygen species (ROS) is crucial. ROS are highly reactive molecules, which contains at least one unpaired electron. They are formed in organism as a natural by-products of aerobic metabolism. Under physiological conditions mitochondria protect cells against ROS trough antioxidants sweeper systems and ATP synthase inhibitor. However, under pathological conditions mitochondria are one of the largest sources of ROS and they are responsible for initiation of cell death. This thesis discusses the changes in cells during the ischemia and following reperfusion. How is ion homeostasis and ATP concentration affected and why the activities of individual complexes of electron-transport chain are decreased.
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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 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 phospholipases A2 and oxidative stress
Závišková, Kristýna ; Míčová, Petra (advisor) ; Chytilová, Anna (referee)
Heart and vascular diseases, in which oxidative stress plays an important role, are the most frequent cause of death in developed countries. Therefore today's researches focus on clarifying signaling pathway and their components that operates in these processes. One of the possible key factors can be phospholipases A2. These enzymes hydrolyze unsaturated fatty acids from C2 position on phospholipids, which easily subject to the oxidative modification due to their double bonds. There are five groups: the secreted, the cytosolic, the calcium independent, the platelet-activating factor acetylhydrolases and the lysosomal phospholipases A2. They differ in the requirement for calcium ions for its activity, molecular weight, position of disulfide bonds and amino acids sequences in the active site. Their main importance is to keep the stability and integrity of cell membranes and produce lipid signaling molecules (free fatty acids, lysophospholipids, eicosanoids). The phospholipases A2 play a dual role during oxidative stress in myocardium. First, they have a positive effect by protecting membranes against oxidative stress due to their higher affinity for removal of peroxidized fatty acids from membrane phospholipids. On the other hand, the phospholipases A2 can also cause destructive effects during...
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Cardioprotective effects of exercise training
Zajíčková, Pavlína ; Neckář, Jan (advisor) ; Míčová, Petra (referee)
Ischemia-reperfusion myocardial injury is one of the main causes of death as a result of cardiovascular disease. Creation of a programme aimed at prevention attracts attention because number of patients suffering from this disease is increasing. One possibility is a regular physical activity whose positive effect on ischemic myocardium has been confirmed by empirical evidence. On the other hand we still do not know what activities are the most suitable and which intensity is the best for our health. Mechanisms which are created by regular exercise and contribute to heart protection have not been fully identified yet. The objective of this paper is to discover potential mechanisms and describe their role in protecting our heart. Moreover, it deals with possible ways of training which could activate such mechanisms and thus reduce significantly the risk of myocardial injury.
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