Effects of anthocyanins and their metabolites on the function of human endothelial cells and platelets in vitro
Uticaj antocijana i njihovih metabolita na funkciju endotelnih ćelija i trombocita čoveka in vitro

2018
Authors
Krga, Irena
Contributors
Glibetić, Marija
Milenković, Dragan

Mandić, Ljuba
Jevđović, Tanja
Beaudoin, Claude
Doctoral thesis (Published version)
Metadata
Show full item recordAbstract
Increasing 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...
Kardiovaskularne 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...
Keywords:
antocijani / metaboliti / endotelna disfunkcija / adhezija monocita za endotelne ćelije / transendotelna migracija / aktivacija trombocita / agregacija trombocita sa leukocitima / platelet activation / platelet-leukocyte aggregation / anthocyanins / metabolites / endothelial dysfunction / monocyte-endothelial cell adhesion / monocyte transendothelial migrationSource:
2018Publisher:
- Univerzitet u Beogradu, Biološki fakultet
URI
http://nardus.mpn.gov.rs/handle/123456789/10767http://eteze.bg.ac.rs/application/showtheses?thesesId=6606
https://fedorabg.bg.ac.rs/fedora/get/o:19403/bdef:Content/download
http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=50912015
http://rimi.imi.bg.ac.rs/handle/123456789/1115
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Institut za medicinska istraživanjaTY - THES AU - Krga, Irena PY - 2018 UR - http://nardus.mpn.gov.rs/handle/123456789/10767 UR - http://eteze.bg.ac.rs/application/showtheses?thesesId=6606 UR - https://fedorabg.bg.ac.rs/fedora/get/o:19403/bdef:Content/download UR - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=50912015 UR - http://rimi.imi.bg.ac.rs/handle/123456789/1115 AB - Increasing 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... AB - Kardiovaskularne 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... PB - Univerzitet u Beogradu, Biološki fakultet T1 - Effects of anthocyanins and their metabolites on the function of human endothelial cells and platelets in vitro T1 - Uticaj antocijana i njihovih metabolita na funkciju endotelnih ćelija i trombocita čoveka in vitro UR - https://hdl.handle.net/21.15107/rcub_nardus_10767 ER -
@phdthesis{ author = "Krga, Irena", year = "2018", abstract = "Increasing 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..., Kardiovaskularne 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...", publisher = "Univerzitet u Beogradu, Biološki fakultet", title = "Effects of anthocyanins and their metabolites on the function of human endothelial cells and platelets in vitro, Uticaj antocijana i njihovih metabolita na funkciju endotelnih ćelija i trombocita čoveka in vitro", url = "https://hdl.handle.net/21.15107/rcub_nardus_10767" }
Krga, I.. (2018). Effects of anthocyanins and their metabolites on the function of human endothelial cells and platelets in vitro. Univerzitet u Beogradu, Biološki fakultet.. https://hdl.handle.net/21.15107/rcub_nardus_10767
Krga I. Effects of anthocyanins and their metabolites on the function of human endothelial cells and platelets in vitro. 2018;. https://hdl.handle.net/21.15107/rcub_nardus_10767 .
Krga, Irena, "Effects of anthocyanins and their metabolites on the function of human endothelial cells and platelets in vitro" (2018), https://hdl.handle.net/21.15107/rcub_nardus_10767 .