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Uticaj antocijana i njihovih metabolita na funkciju endotelnih ćelija i trombocita čoveka in vitro

dc.contributor.advisorGlibetić, Marija
dc.contributor.otherMilenković, Dragan
dc.contributor.otherMandić, Ljuba
dc.contributor.otherJevđović, Tanja
dc.contributor.otherBeaudoin, Claude
dc.creatorKrga, Irena S.
dc.date.accessioned2019-02-26T11:22:25Z
dc.date.available2019-02-26T11:22:25Z
dc.date.available2020-07-03T08:14:26Z
dc.date.issued2018-09-21
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/10767
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=6606
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:19403/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=50912015
dc.description.abstractIncreasing number of scientific evidence suggests the beneficial role of dietary anthocyanins, phytochemicals mainly present in berries and derived products, in cardiovascular health. These anthocyanin health benefits may be attributed to their effect on endothelial cells or platelets that represent the key players in the development of cardiovascular diseases (CVD). However, the exact molecular mechanisms underlying anthocyanin cardioprotective effects are not fully understood. The aim of this thesis was to investigate the effect of anthocyanins and their metabolites in vitro on endothelial and platelet function and identify the underlying mechanisms of their action using physiologically relevant conditions. Results from this thesis showed that the pretreatment of endothelial cells with physiologically relevant concentrations of circulating anthocyanins and their metabolites attenuated monocyte adhesion to activated endothelial cells as well as their transendothelial migration, which are the initial steps in the development of atherosclerosis that precede CVD. In agreement with these results, gene expression analysis revealed that the treatment of endothelial cells with these compounds modulated the expression of genes involved in regulation of cell-cell adhesion, actin cytoskeleton reorganisation, focal adhesion and leukocyte transmigration. Bioinformatics analyses of gene expression data allowed the identification of potential transcription factors involved in the observed nutrigenomic effects and cell signalling proteins regulating their activity. Molecular docking analyses further revealed cell signalling proteins to which these bioactives may bind to and potentially affect their activity and the activation of downstream signalling proteins and transcription factors, effects that were in agreement with the results of Western blot analyses. Anthocyanins and their metabolites also modulated the expression of microRNAs, especially those involved in regulation of endothelial cell permeability, contributing to the observed changes in endothelial cell function...sr
dc.description.abstractKardiovaskularne bolesti predstavljaju oboljenja koja zahvataju srce i krvne sudove i najčešći su uzrok obolevanja i umiranja u svetu. Prema mestu javljanja mogu se podeliti na bolesti srca, cerebrovaskularne bolesti i bolesti perifernih krvnih sudova. Osnovni uzročnik kardiovaskularnih bolesti je ateroskleroza, hronično zapaljensko oboljenje velikih i srednje velikih arterijskih krvnih sudova koje se karakteriše aterosklerotičnim lezijama koje nastaju nakupljanjem lipida, ćelija i proteina vezivnog tkiva unutar zida krvnog suda. Ove patološke promene krvnih sudova ometaju normalan protok krvi, a u kasnijim stadijumima bolesti mogu dovesti i do pucanja plaka i aterotromboze, što za posledicu može imati infarkt miokarda ili šlog. Sam nastanak ateroskleroze povezan je sa poremećenom funkcijom endotela krvnog suda koja podstiče adheziju leukocita za aktivirane endotelne ćelije i njihovu transendotelnu migraciju. Unutar zida krvnog suda monociti se diferenciraju u makrofage, vrše ingestiju oksidovanog LDL holesterola i formiraju penušave ćelije čije nakupljanje vremenom dovodi do formiranja aterosklerotičnih lezija. Važnu ulogu u nastanku ateroskleroze imaju i trombociti. Interakcija aktiviranih trombocita sa leukocitima i endotelnim ćelijama podstiče adheziju leukocita i njihovu transendotelnu migraciju i time dodatno podstiče zapaljenski proces i razvoj ateroskleroze. Stoga, ispitivanje uzajamnog delovanja endotelnih ćelija, leukocita i trombocita predstavlja značajno područje istraživanja u cilju prevencije i kontrole kardiovaskularnih bolesti. Ishrana ima važnu ulogu, kako u nastanku i razvoju kardiovaskularnih bolest, tako i u njihovoj prevenciji i lečenju. Rezultati brojnih epidemioloških i kliničkih studija pokazuju povoljno delovanje ishrane bogate voćem i povrćem na kardiovaskularno zdravlje. Ovo pozitivno delovanje namirnica biljnog porekla pripisuje se delom njihovom niskom energetskom vrednošću, visokom sadržaju vlakana i esencijalnih mikronutrijenata, ali pre svega nenutritivnim, biološki aktivnim sastojcima, poput polifenola...en
dc.formatapplication/pdf
dc.languageen
dc.publisherУниверзитет у Београду, Биолошки факултетsr
dc.rightsopenAccessen
dc.sourceУниверзитет у Београдуsr
dc.subjectanthocyaninssr
dc.subjectantocijanien
dc.subjectmetabolitien
dc.subjectendotelna disfunkcijaen
dc.subjectadhezija monocita za endotelne ćelijeen
dc.subjecttransendotelna migracijaen
dc.subjectaktivacija trombocitaen
dc.subjectagregacija trombocita sa leukocitimaen
dc.subjectmetabolitessr
dc.subjectendothelial dysfunctionsr
dc.subjectmonocyte-endothelial cell adhesionsr
dc.subjectmonocyte transendothelial migrationsr
dc.subjectplatelet activationsr
dc.subjectplatelet-leukocyte aggregationsr
dc.titleEffects of anthocyanins and their metabolites on the function of human endothelial cells and platelets in vitrosr
dc.title.alternativeUticaj antocijana i njihovih metabolita na funkciju endotelnih ćelija i trombocita čoveka in vitroen
dc.typedoctoralThesis
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/3333/IzvestajKomisije19083.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/3332/Disertacija.pdf


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