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Effect of endoglin blockage on inflammation-induced endothelial dysfunction in human aortic endothelial cells
Škubová, Andrea ; Tripská, Katarína (advisor) ; Svobodová, Zuzana (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Title of Diploma Thesis: Effect of endoglin blockage on inflammation-induced endothelial dysfunction in human aortic endothelial cells Author: Andrea Škubová Supervisor of Diploma Thesis: PharmDr. Katarína Tripská, Ph.D. Aim: The aim of this thesis was to describe the effect of TNF-α and LPS-induced inflammation on the expression of endoglin and its transcription factors, the expression of biomarkers of endothelial dysfunction, the levels of soluble endoglin, and the adhesion and transmigration of monocytes through human aortic endothelial cells. We further investigated the effect of endoglin blockage by the monoclonal antibody TRC105 (carotuximab) on these processes. Methods: In this thesis, human aortic endothelial cells (HAEC) were used, and they were exposed for 16 hours to TNF-α (10 ng/ml) and LPS (100 ng/ml) and for 12 hours to TRC105 (300 µg/ml). The mRNA expression of endoglin and its transcription factors (KLF6, RelA, NR1H3), mRNA expression of inflammatory adhesion molecules (ICAM-1, VCAM-1, SELE) and mRNA expression of MMP-14 enzyme were measured by real time qRT-PCR. Using flow cytometry, we detected protein levels of endoglin, protein levels of inflammatory adhesion molecules...
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Effect of endoglin blockage on inflammation-induced endothelial dysfunction in human aortic endothelial cells
Škubová, Andrea ; Tripská, Katarína (advisor) ; Svobodová, Zuzana (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Title of Diploma Thesis: Effect of endoglin blockage on inflammation-induced endothelial dysfunction in human aortic endothelial cells Author: Andrea Škubová Supervisor of Diploma Thesis: PharmDr. Katarína Tripská, Ph.D. Aim: The aim of this thesis was to describe the effect of TNF-α and LPS-induced inflammation on the expression of endoglin and its transcription factors, the expression of biomarkers of endothelial dysfunction, the levels of soluble endoglin, and the adhesion and transmigration of monocytes through human aortic endothelial cells. We further investigated the effect of endoglin blockage by the monoclonal antibody TRC105 (carotuximab) on these processes. Methods: In this thesis, human aortic endothelial cells (HAEC) were used, and they were exposed for 16 hours to TNF-α (10 ng/ml) and LPS (100 ng/ml) and for 12 hours to TRC105 (300 µg/ml). The mRNA expression of endoglin and its transcription factors (KLF6, RelA, NR1H3), mRNA expression of inflammatory adhesion molecules (ICAM-1, VCAM-1, SELE) and mRNA expression of MMP-14 enzyme were measured by real time qRT-PCR. Using flow cytometry, we detected protein levels of endoglin, protein levels of inflammatory adhesion molecules...
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Current trends in dyslipidemia therapy
Krupová, Tatiana ; Nachtigal, Petr (advisor) ; Tripská, Katarína (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Title of Diploma Thesis: Current trends in dyslipidemia therapy Author: Tatiana Krupová Supervisor of Diploma Thesis: prof. PharmDr. Petr Nachtigal, Ph.D Background: The purpose of this diploma thesis is to describe therapeutic options of different types of dyslipidemia with focus on current trends and new discoveries regarding this matter. Main findings: This diploma thesis emphasizes the importance of correct treatment of dyslipidemia using well-known drugs, as well as new groups of medications to enable the prevention of cardiovascular diseases, the main cause of mortality worldwide. Conclusion: The information gathered for this diploma thesis confirms significant progress in the development of new types of treatment, which consequently makes it possible to better prevent complications that are mainly manifested by the development of cardiovascular diseases. Keywords: cholesterol, lipids, lipoproteins, dyslipidemia, coronary heart disease, statins, fibrates, sequestrants, ezetimibe, niacin, omega-3 fatty acids, phytosterols, fiber, PCSK9 inhibitors, bempedoic acid, mipomersen, volanesorsen, lomitapide, evinacumab, inclisiran, LXR agonists
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Effect of dapagliflozin on the expression and function of endoglin and related biomarkers of endothelial dysfunction in human diabetic coronary endothelial cells
Vavreková, Valéria ; Tripská, Katarína (advisor) ; Fikrová, Petra (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Title of Diploma Thesis: Effect of dapagliflozin on the expression and function of endoglin and related biomarkers of endothelial dysfunction in human diabetic coronary artery endothelial cells Author: Valéria Vavreková Supervisor of Diploma Thesis: PharmDr. Katarína Tripská, Ph.D. Aim: The aim of this thesis was to investigate how dapagliflozin affects the expression and function of endoglin (Eng) and related biomarkers of endothelial dysfunction at different times and concentrations in human diabetic cells. Methods: In this thesis, we worked with human diabetic coronary endothelial cells. We premedicated these with dapagliflozin at different times and concentrations, and dimethyl sulfoxide was used as a control. We measured protein expression of Eng and biomarkers of endothelial dysfunction using flow cytometry. We also used flow cytometry to measure the rate of monocyte adhesion to endothelial. Using ELISA, we detected soluble endoglin (sEng) levels. Results: We demonstrated that a 1nM concentration of dapagliflozin during a 12-hour premedication period led to a decrease in protein expression of adhesion molecules. We further showed that protein expression of Eng was also significantly reduced...
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Possible changes of endoglin expression in endothelial cells.
Tripská, Katarína ; Nachtigal, Petr (advisor) ; Mladěnka, Přemysl (referee) ; Vohnout, Branislav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Doctoral Degree Program: Pharmacology and Toxicology Candidate: Mgr. Katarína Tripská Supervisor: prof. PharmDr. Petr Nachtigal, Ph.D. Title of Doctoral Thesis: Possible changes of endoglin expression in endothelial cells Endoglin (Eng) is a co-receptor for ligands of the Transforming Growth Factor β superfamily. Multiple studies have demonstrated that Eng is associated with metabolic syndrome-related pathological conditions, such as hypercholesterolemia, hyperglycemia, hypertension, or obesity. However, the exact role of Eng in these pathologies is still unknown. Therefore, the main purpose of this thesis was to elucidate and summarize the role of membrane and soluble Eng in the selected pathologies associated with metabolic syndrome. We demonstrated that soluble Eng (sEng) levels, together with plasma lipids and markers of inflammation, were reduced after every lipoprotein apheresis in patients with familial hypercholesterolemia. This result, in combination with knowledge acquired by the review article, indicates that increased sEng levels are associated with cardiometabolic disorders. Regarding the role of membrane Eng, we showed that blockage of Eng expression by TRC105 results in a decrease...
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Possible changes of endoglin expression in endothelial cells.
Tripská, Katarína ; Nachtigal, Petr (advisor) ; Mladěnka, Přemysl (referee) ; Vohnout, Branislav (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biological and Medical Sciences Doctoral Degree Program: Pharmacology and Toxicology Candidate: Mgr. Katarína Tripská Supervisor: prof. PharmDr. Petr Nachtigal, Ph.D. Title of Doctoral Thesis: Possible changes of endoglin expression in endothelial cells Endoglin (Eng) is a co-receptor for ligands of the Transforming Growth Factor β superfamily. Multiple studies have demonstrated that Eng is associated with metabolic syndrome-related pathological conditions, such as hypercholesterolemia, hyperglycemia, hypertension, or obesity. However, the exact role of Eng in these pathologies is still unknown. Therefore, the main purpose of this thesis was to elucidate and summarize the role of membrane and soluble Eng in the selected pathologies associated with metabolic syndrome. We demonstrated that soluble Eng (sEng) levels, together with plasma lipids and markers of inflammation, were reduced after every lipoprotein apheresis in patients with familial hypercholesterolemia. This result, in combination with knowledge acquired by the review article, indicates that increased sEng levels are associated with cardiometabolic disorders. Regarding the role of membrane Eng, we showed that blockage of Eng expression by TRC105 results in a decrease...
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Evaluation of antibody quality for Endoglin detection in liver
Kejzlarová, Eliška ; Svobodová, Zuzana (advisor) ; Tripská, Katarína (referee)
The diploma thesis deals with endoglin, a transmembrane glycoprotein that can be cleaved to form so-called soluble endoglin, which then circulates in the blood. The theoretical part of the thesis is devoted to cardiovascular and liver diseases related to changes in the expression or level of endoglin in the blood and summarizes current knowledge about endoglin and its relation to various diseases. The experimental part of the thesis describes the selection of a suitable antibody against endoglin intended for western blot (WB). We have four anti-endoglin primary antibodies available from three manufacturers. The purpose was to test the antibodies and determine, which one had the best ability to detect endoglin in mouse tissue samples such as liver or aorta on WB. Affiblot was used to verify their ability to bind endoglin and also to compare their affinities to this protein. Newly developed patented dot-blot-based device. The binding of the used antibodies to endoglin was verified using the WB method and then the results of both methods were compared. The obtained results showed that the Abcam antibody has the most suitable parameters regarding specificity and sensitivity for the identification of endoglin in mouse tissue on WB. Keywords: endoglin, soluble endoglin, NASH, cirrhosis, non-alcoholic...
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Genetic diseases of the liver
Šepsová, Marika ; Doleželová, Eva (advisor) ; Tripská, Katarína (referee)
Author: Marika Šepsová Title: Genetic diseases of the liver Form: Bachelor Thesis University: Charles University, Faculty of Pharmacy in Hradec Králové Degree: Medical Laboratory Technician Liver function may be affected by various factors including genetic diseases. The aim of this bachelor thesis is to collect and summarize current information about genetic diseases of the liver. Diseases with the highest incidence in the population are Dubin-Johnson syndrome, Rotor syndrome, Crigler-Najjar syndrome and Gilbert's syndrome. They are known as inherited hyperbilirubinemia characterized by an impairment in bilirubin metabolism. These genetic diseases are very rare with exception of Gilbert's syndrome. However, despite low prevalence and incidence it is necessary not to prolong their diagnosis. Most of them do not have any complications and do not require any treatment. The exception is Crigler-Najjar's syndrome, as untreated can have fatal consequences. Wilson's disease and hereditary hemochromatosis are inherited disorders of metal metabolism. Wilson's disease is a rare disease caused by an impairment in copper metabolism. Inherited hemochromatosis causes excessive iron deposition in the liver and other organs. Alpha-1 antitrypsin deficiency is characterized by impaired alpha-1 antitrypsin protein...
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miRNAs as diagnostic markers after treatment with glucocorticoids in rheumatology
Tripská, Katarína ; Pávek, Petr (advisor) ; Doseděl, Martin (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Katarína Tripská Supervisor: prof. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: miRNAs as diagnostic markers after treatment with glucocorticoids in rheumatology MicroRNAs are important class of non-coding RNAs that play important role in modulation of expression of multiple genes at a post-transcriptional level. Their deregulation contributes to many immune disorders including rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. This thesis represents the most recent knowledge about functions of microRNAs in pathogenesis of these disorders and results were obtained by review of scientific literature published on PubMed database. The most perspective microRNAs in rheumatoid arthritis seem to be miR-16, miR-21, miR- 146a, miR-150 a miR-223. In lupus miR-148, miR-126, miR-21, miR-155, miR-125a a miR- 146 will probably find their useage as biomarkers. Systemic sclerosis is less examined diseases and we know most about miR-29 in the disease. Since the research of microRNA as diagnostic biomarkers is only at the beginning, it is most likely, that with the time there will be more and more of new microRNAs helping us clarify pathogenesis of each disorder. We can suppose...
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