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Title:Vplivi strižne napetosti toka krvi na endotelij karotide
Authors:ID Sluga, Manja (Author)
ID Brumen, Milan (Mentor) More about this mentor... New window
ID Fajmut, Aleš (Comentor)
Files:.pdf MAG_Sluga_Manja_2017.pdf (1021,95 KB)
MD5: 923E257455E77EB17B2F60E626AC4978
PID: 20.500.12556/dkum/1ea42945-ba5c-4769-9766-e824bcbfe6c4
 
Language:Slovenian
Work type:Master's thesis/paper
Typology:2.09 - Master's Thesis
Organization:FZV - Faculty of Health Sciences
Abstract:V magistrskem delu najprej sistematično predstavimo poznane mehanizme zaznavanja strižne napetosti, njihov vpliv na endotelij karotide in drugih arterij ter vlogo poznanih mehanizmov na produkcijo dušikovega oksida (NO). Ključni mehanosenzorni kompleksi, ki se aktivirajo ob spremembah strižne napetosti in ki sprožajo različne signalne poti v endotelnih celicah, so ionski kanali, receptorji tirozin kinaze, G-proteini, kaveole, adhezijski proteini, citoskelet, glikokaliks in primarne migetalke. Večjo pozornost v nalogi posvetimo tudi opisom mehanosenzornega kompleksa medceličnih stikov, ki mu je v zadnjem času pripisana vedno večja vloga pri mehanotransdukciji strižne napetosti in aktivaciji anti-aterosklerotičnih signalnih poti. V nadaljevanju obravnavamo matematični model, ki kot mehanotransduktorje vključuje ionske kanale, integrine in receptorje, povezane z G-proteini. Model ovrednotimo z namenom ugotavljanja njegove zmožnosti za reprodukcijo relevantnih izmerjenih podatkov produkcije NO. Ugotovitve primerjamo še z drugim modelom, ki upošteva vpliv zgolj dveh mehanoreceptorjev (integrinov in receptorjev, povezanih z G-proteini), toda podrobneje opisuje vplive kompleksa kalcij/kalmodulin (Ca2+/CaM), encima protein kinaza B (Akt) ter stresnega proteina (Hsp90) na aktivnost encima endotelijska sintaza dušikovega oksida (eNOS). Za razliko od prvega modela drugi ne vključuje inhibitornih vplivov encima protein kinaza C (PKC) in nukleotida cikličnega gvanozin monofosfata (cGMP) na aktivnost eNOS in kodacijo signala Ca2+. Modela sta skladna v tem, da v obeh primerih strižna napetost v endotelijski celici sproži produkcijo inozitol trifosfata (IP3), kar vodi do sproščanja Ca2+ iz znotrajceličnih shramb in do kodacije podobnih signalov Ca2+. V obeh modelih je odziv produkcije NO na strižno napetost dvofazen, pri čemer je za pojav druge faze bistvenega pomena signalna pot, ki vključuje encima fosfoinozitid 3-kinazo (PI3K) in Akt. Oba encima imata ključno vlogo pri fosforilaciji encima eNOS, ki je potrebna za dosego njegove največje aktivnosti. Čeprav noben izmed modelov ni povsem popoln, pa vsak izmed njiju omogoča poglobljen in sistematičen vpogled v razumevanje kompleksnih biokemijskih procesov, ki jih lahko sproži strižna napetost v karotidi, in hkratno kvantitativno ovrednotenje pomembnosti posameznih signalnih poti in procesov.
Keywords:strižna napetost, endotelij, mehanotransdukcija, mehanosenzorni kompleks, dušikov oksid, matematični model
Place of publishing:Maribor
Publisher:[M. Sluga]
Year of publishing:2017
PID:20.500.12556/DKUM-68667 New window
UDC:616.12(043.2)
COBISS.SI-ID:2385828 New window
NUK URN:URN:SI:UM:DK:XN4WARFU
Publication date in DKUM:23.02.2018
Views:1972
Downloads:176
Metadata:XML DC-XML DC-RDF
Categories:FZV
:
SLUGA, Manja, 2017, Vplivi strižne napetosti toka krvi na endotelij karotide [online]. Master’s thesis. Maribor : M. Sluga. [Accessed 22 April 2025]. Retrieved from: https://dk.um.si/IzpisGradiva.php?lang=eng&id=68667
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Licences

License:CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Link:http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:06.10.2017

Secondary language

Language:English
Title:Shear stress effects of blood flow on the carotid endothelium
Abstract:In this master thesis systematic descriptions of known mechanisms of shear stress detection, their effect on the endothelium of the carotid and other arteries, as well as the role of known mechanisms on the production of nitric oxide (NO) are presented. The key mechanosensing complexes that respond to changes in shear stress and which trigger different signalling pathways in endothelial cells are: ion channels, tyrosine kinase receptors, G-protein coupled receptors (GPCR), kaveoles, adhesion proteins, cytoskeleton, glycocalyx and primary cilia. More attention was paid to the description of intercellular coupling, which has an increasing role in mechanotransduction of shear stress and activation of anti-atherosclerotic signalling pathways. Further, we present a mathematical model that includes ion channels, integrins and GPCR as mechanosensors. The model is evaluated in order to determine its ability to reproduce the relevant measured data on the NO production. That model is compared with another model that takes into account the influence of two mechanosensors (integrins and GPCR) but includes a more detailed description of the effects of calcium/calmodulin (Ca2+/CaM) complex, protein kinase B (Akt) and heat-shock protein (Hsp90) on the activity of the enzyme endothelial nitric oxide synthase (eNOS). The latter does not include the inhibitory effect of the enzyme protein kinase C (PKC) and the nucleotide cyclic guanosine monophosphate (cGMP) on the activity of eNOS and the encoding of Ca2+ signal. In both models shear stress triggers the production of inositol tris-phosphate (IP3), leading to the release of Ca2+ from intracellular stores and to the encoding of similar Ca2+ signals. In both models, the NO production profile is biphasic, whereby the signalling pathway involving the phosphoinositide 3-kinase (PI3K) and the enzyme Akt are essential for the occurrence of the second phase. It is found out that these two enzymes play a key role in the phosphorylation of the eNOS enzyme needed to achieve its maximal activity. Although none of the models is complete, they provide an in-depth and systematic insight into the understanding of complex biochemical processes that are triggered by shear stress in carotid artery. And, moreover, they both allow quantitative evaluation of the significance of individual signalling pathways and processes.
Keywords:shear stress, endothelium, mechanotransduction, mechanosensory complex, nitric oxide, mathematical model


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