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dc.contributor.advisorKealey, Carmel
dc.contributor.advisorBrady, Damien
dc.contributor.authorKielty, Catriona
dc.date.accessioned2022-07-06T15:48:54Z
dc.date.available2022-07-06T15:48:54Z
dc.date.copyright2021
dc.date.issued2021-04
dc.identifier.citationKielty, C. (2021). An investigation of the in vitro effects of unconjugated linoleic acid and its potential impact on haemostasis. Thesis (Doctor of Philosophy - PhD). Athlone Institute of Technology.en_US
dc.identifier.urihttp://research.thea.ie/handle/20.500.12065/4020
dc.description.abstractIntroduction: Linoleic acid, an essential ω6 fatty acid, is the most abundant polyunsaturated fatty acid in the Western mammalian diet. Linoleic acid has been linked with an increased inflammatory response. It has also been associated with platelet inhibition and with a reduction in platelet thromboxane. Excessive unresolved inflammation can lead to uncontrolled tissue damage and has been associated with several inflammatory mediated diseases. Plasma free fatty acids are known to increase in several disease states as well as during fasting and strenuous exercise. As such, this investigation aimed to elucidate the potential mechanisms by which linoleic acid at supraphysiological concentrations may impact cell health in the liver and the vasculature. Methods: In vitro investigations were used to determine the effects of increasing concentrations of ULA on the inflammatory response. Assays were performed using the human hepatoma cell line, HepG2 and the human umbilical vein endothelial cell line HUVEC. The effects of supraphysiological concentrations of ULA over 8 hours of exposure were assessed. Both cell lines were assayed for the effects of ULA on cell viability and intracellular lipid accumulation. ELISA was used to determine the effects of ULA on thromboxane A2 and TNF-α production. Cell lysates were assayed for the presence of superoxide dismutase (SOD). HepG2 cells were also analysed for ULA induced apoptosis and necrosis using flowcytometry. Results: Treatment concentrations of 1mM and 2.5mM of ULA induced a significant reduction in cell viability even after 1 hour of treatment in both cell lines. The ability of both cell lines to sequester ULA intracellularly at these concentrations was also significantly reduced compared to cells treated with the more physiologically comparable 0.1mM. HepG2 cells treated with 1mM and 2.5mM of ULA presented with a significant reduction in the presence of SOD after 4 hours. However, ULA had no significant effect on the presence of SOD in HUVEC cells. HepG2 cells also presented with increased apoptosis and necrosis at these concentrations after 4 hours of treatment. HUVEC cells treated with 1mM and 2.5mM of ULA showed a significant increase in thromboxane A2 secretion. However, no significant effect on thromboxane A2 production was observed in HepG2 cells. Conclusion: The data suggests that ULA, at supraphysiological concentrations induces cell dysfunction in a number of ways depending on cell type. While Linoleic acid may not directly induce specific disease states, in a system compromised by disease or physiological stress, increasing plasma concentrations of linoleic acid, leading to increasing ROS and diminished antioxidant capabilities may initiate or further exacerbate pathophysiology.en_US
dc.formatPDFen_US
dc.language.isoengen_US
dc.publisherAthlone Institute of Technologyen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectUnconjugated linoleic aciden_US
dc.subjectHaemostasisen_US
dc.titleAn investigation of the in vitro effects of unconjugated linoleic acid and its potential impact on haemostasisen_US
dc.typeinfo:eu-repo/semantics/doctoralThesisen_US
dc.contributor.affiliationAthlone Institute of Technologyen_US
dc.identifier.orcidhttps://orcid.org/ 0000-0002-5203-0995en_US
dc.rights.accessrightsinfo:eu-repo/semantics/openAccessen_US


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Attribution-NonCommercial-NoDerivatives 4.0 International
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