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
Author
Krga, Irena S.Mentor
Glibetić, MarijaCommittee members
Milenković, DraganMandić, Ljuba
Jevđović, Tanja
Beaudoin, Claude
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...