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Molecular mechanisms of LDL-cholesterol induced endothelial dysfunction
Rojková, Tereza ; Petrezsélyová, Silvia (advisor) ; Šeda, Ondřej (referee)
Hypercholesterolemia, defined as elevated LDL-cholesterol levels in the blood, develops either as a result of genetic predispositions, unhealthy lifestyle, underlying diseases, or as a result of a combination of these factors. LDL-cholesterol is sometimes called "bad" cholesterol because its excess negatively affects the vessel`s innermost layer - endothelium, Endothelium is unique for its vasodilatory, vasoconstrictive, anti-inflammatory, and anti- coagulant function but also for its ability to control vascular permeability. In the case of hypercholesterolemia, cholesterol gradually accumulates in the subendothelial space and reduces levels of the main modulatory molecule of the endothelium - nitric oxide by several mechanisms. In endothelial dysfunction, oxidative stress increases, LDL-cholesterol is oxidized, endothelial cells are activated and produce proinflammatory cytokines and adhesive molecules. Endothelial dysfunction is considered the first stage of atherosclerosis, as monocytes enter the site of inflammation and differentiate into macrophages, which subsequently turn into foam cells by endocytosis of oxidized LDL-cholesterol. In this way, atherosclerotic plaques are formed, which not only narrow the blood vessels, but plaques can erupt, causing subsequent thrombosis, which can result...
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Dysregulation of E3 ubiquitin ligases in inflammatory bowel diseases
Armerová, Eliška ; Petrezsélyová, Silvia (advisor) ; Červená, Klára (referee)
E3 ubiquitin ligases are a large family of enzymes involved in many cellular processes such as DNA damage repair, transport of membrane proteins, chromatin modification, cell cycle and apoptosis. E3 ubiquitin ligases have been shown to play a significant role in the maintenance of intestinal homeostasis, and their abnormal function associated with their deregulation contributes to inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. In recent years, GWAS has identified approximately 200 risk loci that are susceptible to these diseases. Including those encoding E3 ubiquitin ligases.The aim of this work is to compare the already identified E3 ubiquitin ligases associated with these diseases and to give an overview of them with a focus on the regulation of intestinal homeostasis. Key words: E3, ubiquitination, inflammatory bowel diseases, intestinal homeostasis, CD, UC
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Dysregulation of E3 ubiquitin ligases in inflammatory bowel diseases
Armerová, Eliška ; Petrezsélyová, Silvia (advisor) ; Červená, Klára (referee)
E3 ubiquitin ligases are a large family of enzymes involved in many cellular processes such as repair of damaged DNA, transport of membrane proteins, chromatin modification, cell cycle and apoptosis. E3 ubiquitin ligase has been shown to play a significant role in the maintenance of intestinal homeostasis, and their abnormal function associated with their deregulation contributes to inflammatory bowel diseases such as ulcerative colitis and Crohn's disease. In recent years, approximately 200 risk loci have been identified that are susceptible to these diseases, including those encoding E3 ubiquitin ligase. 10 of them have been identified. The aim of this work is to compare the already identified E3 ubiquitin ligases associated with these diseases and to give an overview of them with a focus on the regulation of intestinal homeostasis. Key words: E3, ubiquitination, inflammatory bowel diseases, intestinal homeostasis, CD, UC
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