Modulation of cholesterol and bile acid metabolism via soluble endoglin and pharmacotherapy

• Název práce v češtině: Modulace metabolismu cholesterolu a žlučových kyselin prostřednictvím solubilního endoglinu a farmakoterapie.
• Název v anglickém jazyce: Modulation of cholesterol and bile acid metabolism via soluble endoglin and pharmacotherapy
• Akademický rok vypsání: 2018/2019
• Typ práce: disertační práce
• Jazyk práce: angličtina
• Ústav: Katedra biologických a lékařských věd (16-16150)
• Vedoucí / školitel: prof. PharmDr. Petr Nachtigal, Ph.D.
• Řešitel: skrytý - zadáno a potvrzeno stud. odd.
• Datum přihlášení: 01.10.2018
• Datum zadání: 01.10.2018
• Datum potvrzení stud. oddělením: 17.12.2018
• Datum a čas obhajoby: 22.09.2022 13:30
• Datum odevzdání elektronické podoby: 14.07.2022
• Datum odevzdání tištěné podoby: 21.09.2022
• Datum proběhlé obhajoby: 22.09.2022
• Oponenti: prof. MUDr. Libor Vítek, Ph.D.

Zásady pro vypracování

Literature review
Work in the lab
Presentation of results
Publication of results
Thesis defense

Seznam odborné literatury

1. Jezkova K, Rathouska J, Nemeckova I, Fikrova P, Dolezelova E, et al. (2016) High Levels of Soluble Endoglin Induce a Proinflammatory and Oxidative-Stress Phenotype Associated with Preserved NO-Dependent Vasodilatation in Aortas from Mice Fed a High-Fat Diet. J Vasc Res 53: 149-162.
2. Gallardo-Vara E, Blanco FJ, Roque M, Friedman SL, Suzuki T, et al. (2016) Transcription factor KLF6 upregulates expression of metalloprotease MMP14 and subsequent release of soluble endoglin during vascular injury. Angiogenesis 19: 155-171.
3. Zemankova L, Varejckova M, Dolezalova E, Fikrova P, Jezkova K, et al. (2015) Atorvastatin-induced endothelial nitric oxide synthase expression in endothelial cells is mediated by endoglin. J Physiol Pharmacol 66: 403-413.
4. Rathouska J, Jezkova K, Nemeckova I, Zemankova L, Varejckova M, et al. (2015) Endoglin is not expressed with cell adhesion molecules in aorta during atherogenesis in apoE-deficient mice. Histol Histopathol 30: 233-244.
5. Nemeckova I, Serwadczak A, Oujo B, Jezkova K, Rathouska J, et al. (2015) High soluble endoglin levels do not induce endothelial dysfunction in mouse aorta. PLoS One 10: e0119665.
6. La Sala L, Pujadas G, De Nigris V, Canivell S, Novials A, et al. (2015) Oscillating glucose and constant high glucose induce endoglin expression in endothelial cells: the role of oxidative stress. Acta Diabetol 52: 505-512.
7. Kobayashi Y, Yamamoto T, Chishima F, Takahashi H, Suzuki M (2015) Autoantibodies isolated from patients with preeclampsia induce soluble endoglin production from trophoblast cells via interactions with angiotensin II type 1 receptor. Am J Reprod Immunol 73: 285-291.
8. del Castillo G, Sanchez-Blanco E, Martin-Villar E, Valbuena-Diez AC, Langa C, et al. (2015) Soluble endoglin antagonizes Met signaling in spindle carcinoma cells. Carcinogenesis 36: 212-222.
9. Xu G, Barrios-Rodiles M, Jerkic M, Turinsky AL, Nadon R, et al. (2014) Novel protein interactions with endoglin and activin receptor-like kinase 1: potential role in vascular networks. Mol Cell Proteomics 13: 489-502.
10. Verlohren S (2014) Re: Longitudinal changes in maternal soluble endoglin and angiopoietin-2 in women at risk for pre-eclampsia. A. Khalil, N. Maiz, R. Garcia-Mandujano, M. Elkhouli and K. H. Nicolaides. Ultrasound Obstet Gynecol 2014; 44: 402-410. Ultrasound Obstet Gynecol 44: 386.
11. Tseliou E, Reich H, de Couto G, Terrovitis J, Sun B, et al. (2014) Cardiospheres reverse adverse remodeling in chronic rat myocardial infarction: roles of soluble endoglin and Tgf-beta signaling. Basic Res Cardiol 109: 443.
12. Tobar N, Avalos MC, Mendez N, Smith PC, Bernabeu C, et al. (2014) Soluble MMP-14 produced by bone marrow-derived stromal cells sheds epithelial endoglin modulating the migratory properties of human breast cancer cells. Carcinogenesis 35: 1770-1779.
13. Perucci LO, Gomes KB, Freitas LG, Godoi LC, Alpoim PN, et al. (2014) Soluble endoglin, transforming growth factor-Beta 1 and soluble tumor necrosis factor alpha receptors in different clinical manifestations of preeclampsia. PLoS One 9: e97632.
14. Olsen OE, Wader KF, Misund K, Vatsveen TK, Ro TB, et al. (2014) Bone morphogenetic protein-9 suppresses growth of myeloma cells by signaling through ALK2 but is inhibited by endoglin. Blood Cancer J 4: e196.
15. Meurer SK, Alsamman M, Scholten D, Weiskirchen R (2014) Endoglin in liver fibrogenesis: Bridging basic science and clinical practice. World J Biol Chem 5: 180-203.
16. Liu Y, Starr MD, Brady JC, Dellinger A, Pang H, et al. (2014) Modulation of circulating protein biomarkers following TRC105 (anti-endoglin antibody) treatment in patients with advanced cancer. Cancer Med 3: 580-591.
17. Kumar S, Pan CC, Bloodworth JC, Nixon AB, Theuer C, et al. (2014) Antibody-directed coupling of endoglin and MMP-14 is a key mechanism for endoglin shedding and deregulation of TGF-beta signaling. Oncogene 33: 3970-3979.
18. Khalil A, Maiz N, Garcia-Mandujano R, Elkhouli M, Nicolaides KH (2014) Longitudinal changes in maternal soluble endoglin and angiopoietin-2 in women at risk for pre-eclampsia. Ultrasound Obstet Gynecol 44: 402-410.
19. Kaitu'u-Lino TJ, Tong S, Beard S, Hastie R, Tuohey L, et al. (2014) Characterization of protocols for primary trophoblast purification, optimized for functional investigation of sFlt-1 and soluble endoglin. Pregnancy Hypertens 4: 287-295.
20. Jang YS, Choi IH (2014) Contrasting roles of different endoglin forms in atherosclerosis. Immune Netw 14: 237-240.
21. Hastie R, Tong S, Cannon P, Brownfoot F, Hannan NJ, et al. (2014) Peptides do not prevent cleavage of endoglin to produce soluble endoglin. Pregnancy Hypertens 4: 255-258.
22. Gregory AL, Xu G, Sotov V, Letarte M (2014) Review: the enigmatic role of endoglin in the placenta. Placenta 35 Suppl: S93-99.
23. Brownfoot FC, Hannan N, Onda K, Tong S, Kaitu'u-Lino T (2014) Soluble endoglin production is upregulated by oxysterols but not quenched by pravastatin in primary placental and endothelial cells. Placenta 35: 724-731.

Předběžná náplň práce

PhD thesis will be focused on study of soluble endoglin effects on cholesterol and bile acid metabolism in various conditions including high fat diet administration, hypolipidemic and antidiabetic treatment in experimental mice. The endoglin related and pathways related to cholesterol and bile acid metabolism will be evaluated by means of rt-PCR, Western blot analysis, ELISA analysis and functional studies of cholesterol metabolism and bile elimination in liver small intestine. The results will be presented in scientific congresses and meetings and published in journal with impact factor.

Předběžná náplň práce v anglickém jazyce

PhD thesis will be focused on study of soluble endoglin effects on cholesterol and bile acid metabolism in various conditions including high fat diet administration, hypolipidemic and antidiabetic treatment in experimental mice. The endoglin related and pathways related to cholesterol and bile acid metabolism will be evaluated by means of rt-PCR, Western blot analysis, ELISA analysis and functional studies of cholesterol metabolism and bile elimination in liver small intestine. The results will be presented in scientific congresses and meetings and published in journal with impact factor.