o:39162 Uticaj endokrinih ometača, bisfenola A i dibutil-ftalata, na funkciju humanih endotelnih ćelija u uslovima in vitro doktorska disertacija Impact of in vitro exposure to endocrine disrupting chemicals bisphenol A and dibutyl phthalate on the function of human endothelial cells : doctoral dissertation sr Bisfenol A (BPA) i dibutil-ftalat (DBP) su prisutni u mnogim proizvodima koje čovek svakodnevno koristi. Negativan uticaj ovih hemikalija na endokrini i reproduktivni sistem je dobro ispitan, ali su podaci o njihovom uticaju na kardiovaskularni sistem oskudni. Cilj ove doktorske disertacije je da se ispitaju funkcijske i molekulske promene na humanim endotelnim ćelijama EA.hy926 koje se javljaju kao odgovor na dugotrajno (12-14 nedelja) izlaganje ćelija 10-9, 10-8 i 10-7 М BPA i DBP i kratkotrajno (15 min – 48 h) izlaganje 10-7, 10-6 i 10-5 M BPA i 10-6, 10-5 i 10-4 M DBP u uslovima in vitro.Dugotrajno i kratkotrajno izlaganje EA.hy926 ćelija BPA dovodi do funkcijskih i molekulskih promena koje pospešuju integritet endotela u uslovima in vitro: smanjeno vezivanje monocita za endotelne ćelije preko smanjenja relativne ekspresije gena za adhezivni molekul VCAM-1, povećana adhezija ćelija za želatin i smanjena migracija, smanjena propustljivost jednosloja endotelnih ćelija uz povećanu ekspresiju okludina i ZO-1, kao i smanjeni nivo ROS, uz istovremeno povećano stvaranje NO preko ER i GPER i nizvodno aktivacijom signalnog puta PI3K/Akt i eNOS.Dugotrajno i kratkotrajno izlaganje EA.hy926 ćelija DBP dovodi do funkcijskih i molekulskih promena koje narušavaju integritet endotela u uslovima in vitro: povećano vezivanje monocita za endotelne ćelije, promene u migraciji ćelija i angiogenezi, promene u propustljivosti jednosloja endotelnih ćelija uz odgovarajuće promene u ekspresiji okludina i ZO-1, kao i povećano stvaranje NO preko ER i GPER i nizvodne aktivacije signalnih puteva PI3K/Akt, MAPK/ERK i eNOS. Utvrđeno je da ovi mehanizmi imaju ulogu u angiogenezi i migraciji ćelija, za koju je pokazano da se dešava uz povećanu aktivnost enzima MMP-2. Bisphenol A (BPA) and dibutyl phthalate (DBP) are present in many products people use daily. The negative impact of BPA and DBP on the endocrine and reproductive systems is well documented; however, the data regarding their impact on the cardiovascular system are scarce. The goal of this Doctoral Dissertation was to investigate whether in vitro long-term (12-14 weeks) exposure to 10-9, 10-8, and 10-7 М BPA and DBP and short-term (15 min – 48 h) exposure to 10-7, 10-6, and 10-5 M BPA and 10-6, 10-5, and 10-4 M DBP affects the functional and molecular properties of EA.hy926 cells.Long-term and short-term exposure of EA.hy926 cells to BPA induces functional and molecular changes that promote endothelial integrity: decreased adhesion of monocytes to endothelial cells via decreased relative expression of VCAM-1, increased cell adhesion to gelatin and decreased migration, diminished endothelial permeability accompanied with increased expression of occludin and ZO-1, lower ROS levels, and increased NO synthesis via ER and GPER and downstream activation of the PI3K/Akt pathway and eNOS.Long-term and short-term exposure of EA.hy926 cells to DBP induces functional and molecular changes that disrupt endothelial integrity: increased adhesion of monocytes to endothelial cells, alterations in cell migration and angiogenesis, changes in the permeability of the endothelial monolayer with relevant changes in the expression of occludin and ZO-1, as well as an increase in NO synthesis via ER and GPER and downstream activation of PI3K/Akt and ERK1/2 pathways and eNOS. It was concluded that these mechanisms have a role in the regulation of angiogenesis and cell migration, which was confirmed to occur with an increase in MMP-2 activity. Biologija - Molekularna biologija eukariota / Biology - Molecular Biology of Eukaryotes Datum odbrane: 16.12.2025. endotelne ćelije, bisfenol A, dibutil-ftalat, endotelna disfunkcija endothelial cells, bisphenol A, dibutyl phthalate, endothelial dysfunction 577.2:577.1(043.3) 91552100 193857801 91552101 10416 2026-06-03T10:05:50.053Z 45 no 46 Dunja, 1991- Kokai 137476105 2025 63 mentor Bojana, 1975- Stanić 128537865 2025 63 mentor Jelena, 1964- Đorđević 12655207 2025 63 član komisije Nebojša, 1971- Andrić 12976487 2025 63 član komisije Jelena, 1984- Marković Filipović 22570087 2025 63 član komisije Dušanka, 1972- Savić-Pavićević 12846951 2025 164 str. 11002009 http://phaidrabg.bg.ac.rs/o:39162 no yes 12 2026-06-03T10:05:50.320Z 70 11 1066841 1066867 endotelne ćelije, bisfenol A, dibutil-ftalat, endotelna disfunkcija endothelial cells, bisphenol A, dibutyl phthalate, endothelial dysfunction 577.2:577.1(043.) 1738 11A02 2025