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Reverse cholesterol transport determine in vivo
Coufalíková, Martina ; Poledne, Rudolf (advisor) ; Svoboda, Petr (referee)
Prague hereditary hypercholesterolemic (PHHC) rat is a specie, which is very sensitive to a dietary cholesterol. Our study deals with characteristics of nascent VLDL particles and introduces new method for measurements of reverse cholesterol transport in vivo on rats. Characteristics of nascent VLDL particles Production of VLDL particles was studied with two different rat species - Wistar and PHHC. VLDL particles were isolated from a serum 2 hours after i.v. application of Triton WR 1339. No dependence of cholesteromie of the Wistar rats on the diet was observed, while increase of about 45 % of cholesterol of PHHC rats was found. The count of triglycerides (TG) after application of tyloxapol steeply increased as a result of accumulation of VLDL particles. Small increase of cholesterol in VLDL particles was observed assuming Wistar rats on the cholesterol diet, while the same increase was found to be rapidly higher with PHHC rats on the same diet. Liver of PHHC rats on the cholesterol diet therefore products nascent VLDL particles significantly enriched with cholesterol. Measurements of reverse cholesterol transport in vivo Primary cell culture of macrophages obtained by the help of peritoneal lavage was incubated for 48 hours with 3H cholesterol and then intraperitoneally applicated to Wistar and PHHC rats....
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The importance of the expression of leukocyte and thrombogenic markers in the atherogenesis
Svobodová, Helena ; Štulc, Tomáš (advisor) ; Maruna, Pavel (referee) ; Poledne, Rudolf (referee)
Inflammatory and prothrombotic factors play a crucial role in the atherogenesis. Dyslipidemia and diabetes mellitus as well are associated with the endothelial and leukocyte activation, which facilitate the inflammatory infiltration of the subendothelial space and deteriorate endothelial dysfunction, and thus contribute to the development of premature atherosclerosis. Furthermore, diabetes is associated with a number of platelets and coagulation factors abnormalities that participate in atherogenesis by other mechanisms and may be involved in the acute atherothrombotic events progression. Therefore, the factors that could favourably influence these actions become the subject of interest. In this work, we examined leukocyte expression of cell adhesion molecules in patients with hypercholesterolemia and type 2 diabetes, and thrombogenic molecules on leukocytes in type 2 diabetes, and also soluble endothelial and thrombogenic markers. In these patient groups, we investigated the effect of lipid lowering and antidiabetic treatment on these markers. (...) In contrast, there was nearly no effect of the hypolipidemic and antidiabetic treatment on the serum/plasma endothelial and thrombogenic molecules. Leukocyte molecules may therefore be a more sensitive marker of atherogenesis than circulating endothelial...
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Šejda, Tomáš ; Poledne, Rudolf (advisor) ; Filipovský, Jan (referee) ; Češka, Richard (referee)
Based on the results of our study, we concluded that the degree of brachial artery flow endothelium-dependent dilatation is difficult to evaluate using predefined cut-off points as a single-measurement screening test to indicate endothelial dysfunction. On the contrary, the variation of endothelial function after a defined stimulus (dietary, medication) examined at a predefined interval using an identical protocol can help to assess enhanced or reduced efficacy of endothelium-dependent vasodilatation. In the next study, we demonstrated that a high-fat load applied at a single dose does not significantly affect brachial artery vasoreactivity in young, healthy volunteers after four weeks of low- and high-fat diets. In contrast with atherosclerosis, the effect of hypercholestrolemia on adhesive molecule levels has been a source of controversy. We demonstrated that 3-month therapy with fluvastatin does not decrease cICAM-1 levels despite normalization of cholesterol levels. The implication is cholesterol may not induce endothelial activation by the initial upregulation of this adhesive molecule. Endothelial dysfunction can be considered the initial, functionally relevant stage of atherosclerosis, demonstrable still before morphological changes. In patients with advanced obliterative atherosclerosis,...
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