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Studying of atorvastatin effects on atherogenesis in apoE-/-/LDLR-/- double knock-out mouse model of atherosclerosis I.
Stráský, Zbyněk ; Nachtigal, Petr (advisor) ; Štěrba, Martin (referee)
Atherosclerosis, or sclerosis of arteries, is a degenerative disease of arteries. Sometimes it is called "the disease of 20th century". ApoE/LDL - receptor double knockout mice represent a new animal model for study of atherogenesis, which is characterized by severe hyperlipidaemia and atherosclerosis. Statins (or competitive inhibitors 3-hydroxyl-3-methyl-glutaryl-coenzym Areductase) currently belong to the most efficient and the most useful hypolipidemic drugs for all over the world. They decrease mainly levels of total cholesterol and LDL cholesterol. The aim of this thesis was to describe the expression of endoglin in atherosclerotic plaques in apoE/LDL-receptor deficient mice. Moreover we wanted to determine the effect of atorvastatin treatment on the expression of both endoglin.. ApoE/LDLR-deficient mice on were subdivided into 2 groups. The control group of animals was fed with the western type diet. The same atherogenic diet was used in ATV group, where atorvastatin was added to the atherogenic diet at the dosage of 100 mg/kg per day. The results of this thesis confirmed the expression of endoglin in atherosclerotic lesions in ApoE/LDLR-deficient mice. The expression of endoglin was located on the aortic vascular endothelium and in other smaller vessels and capillaries of surrounding...
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Possibilities to Influence Atherogenesis in Experimental Animal Models and Endothelial Cells
Stráský, Zbyněk ; Nachtigal, Petr (advisor) ; Blaha, Vladimír (referee) ; Kazdová, Ludmila (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Candidate: Mgr. Zbyněk Stráský Supervisor: Doc. PharmDr. Petr Nachtigal, Ph.D. Title of Doctoral Thesis: Possibilities to influence atherogenesis in experimental animal models and endothelial cells. This guided final thesis studied the Endoglin and Spirulina platensis in the process of atherosclerosis both in vivo and in vitro and their effects on specific pro- or anti-atherogenic markers, particularly with regard to the vascular endothelium. Endoglin (CD 105, TGF-β receptor III ENG) is a homodimeric membrane glycoprotein, which plays a regulatory role in TGFβ signaling. The relation between endoglin and endothelial NO synthase (eNOS) is essential for our study. Endoglin increases eNOS expression and promotes the production of NO, which affects the function of vascular endothelium. Changes in the expression of eNOS and endoglin could thus be associated with the development of endothelial dysfunction, a key step in atherogenesis. In our studies, we investigated the effects of cholesterol (1% cholesterol diet) and statins (atorvastatin) with respect to endoglin expression and soluble endoglin levels in a mouse model of atherosclerosis. Hypercholesterolemia increased levels of soluble...
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Studying of atorvastatin effects on atherogenesis in apoE-/-/LDLR-/- double knock-out mouse model of atherosclerosis I.
Stráský, Zbyněk ; Nachtigal, Petr (advisor) ; Štěrba, Martin (referee)
Atherosclerosis, or sclerosis of arteries, is a degenerative disease of arteries. Sometimes it is called "the disease of 20th century". ApoE/LDL - receptor double knockout mice represent a new animal model for study of atherogenesis, which is characterized by severe hyperlipidaemia and atherosclerosis. Statins (or competitive inhibitors 3-hydroxyl-3-methyl-glutaryl-coenzym Areductase) currently belong to the most efficient and the most useful hypolipidemic drugs for all over the world. They decrease mainly levels of total cholesterol and LDL cholesterol. The aim of this thesis was to describe the expression of endoglin in atherosclerotic plaques in apoE/LDL-receptor deficient mice. Moreover we wanted to determine the effect of atorvastatin treatment on the expression of both endoglin.. ApoE/LDLR-deficient mice on were subdivided into 2 groups. The control group of animals was fed with the western type diet. The same atherogenic diet was used in ATV group, where atorvastatin was added to the atherogenic diet at the dosage of 100 mg/kg per day. The results of this thesis confirmed the expression of endoglin in atherosclerotic lesions in ApoE/LDLR-deficient mice. The expression of endoglin was located on the aortic vascular endothelium and in other smaller vessels and capillaries of surrounding...
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