@misc{Sroczyńska_Katarzyna_The_2022,
 author={Sroczyńska, Katarzyna},
 address={Kraków},
 howpublished={online},
 year={2022},
 school={Wydział Farmaceutyczny},
 language={pol},
 abstract={Endothelial cells are characterized by intense metabolic activity. They participate in maintaining the body's homeostasis, including blood pressure control (vasoconstriction and vasodilation), oxygen concentration, blood coagulation regulation, energy balance control, and also in the process of angiogenesis. The main factors causing dysfunction and, as a result, vascular endothelial diseases are a poorly balanced diet and an incorrect lifestyle. Dysfunction of endothelium is accompanied by an imbalance between the vasodilators and vasoconstrictors synthesis. As a result, there is an increased synthesis of reactive nitrogen and oxygen species, activation of the inflammatory reaction, damage, and aging of cells. The factor causing the development of the pathological condition within the cardiovascular system is chronic inflammation due to the lack of an effective mechanism of resolution of inflammation and the process of tissue healing. Polyunsaturated fatty acids and their derivatives are pharmacologically active lipid mediators, which play an essential role in the body's physiological and pathological processes. The active lipid mediators of n-3 and n-6 polyunsaturated fatty acids, belong to the compounds involved in the resolution of inflammation. Supplementation with n-3 fatty acids has an antioxidant and protective effect on the cardiovascular system thanks to the biosynthes},
 abstract={is of specific anti-inflammatory mediators. However, the role of de novo synthesis and uptake of exogenous fatty acids by endothelial cells in inflammatory conditions is not well understood and elucidated. Expanding the current knowledge could contribute to developing new anti-inflammatory drugs and therapeutic strategies for the efficient, targeted metabolism of fatty acids in the endothelium under conditions of inflammation. Thus, it justifies undertaking research in this direction. This doctoral thesis aimed to determine whether fatty acids of the n-6 series (γ-linolenic acid GLA, arachidonic acid ARA), n-3 series (eicosapentaenoic acid EPA), and lovastatin can activate the defense mechanisms of endothelial cells (human primary umbilical vein endothelial cells, HUVEC), activated with inflammatory factors (lipopolysaccharide, LPS; tumor necrosis factor-α, TNF-α; and benzo(a)pyrene, BaP). The above goal was achieved by analyzing the fatty acid profile of cell membranes and the expression of proteins and genes related to inflammation. Endothelial cells were incubated with arachidonic acid (ARA, n-6), γ-linolenic acid (GLA, n-6) or with eicosapentaenoic acid (EPA, n-3) and lovastatin (LOVA), and activated with inflammatory factors. Significant differences were demonstrated in the fatty acid profile of the cell membranes after incubation with ARA or EPA and incubation with LPS},
 abstract={or BaP. Supplementation of HUVEC cells with EPA or ARA and LPS activation resulted in statistically significant repression of pro-inflammatory proteins COX-2, cPGES (prostaglandin E2 synthase), and receptor for prostaglandin F2α (FP receptor) as well as the isoprostane 8-isoPGF2α content. A decrease in COX-1, COX-2, phospholipase A2 (cPLA2), and toll-like receptor 4 (TRL4) proteins was observed in HUVEC cells after incubation with GLA and LOVA, despite TNF-α activation. There was an increase in the level of aromatic hydrocarbon receptor (AHR) after previous ARA and EPA supplementation and BaP activation, while an increase in M1 glutathione transferase (GSTM1) was noted only in the case of supplementation of endothelial cells with EPA and activation of BaP. Decreased mRNA levels for cytochrome P450 CYP1A1, phospholipase A2 (PLA2G4A), and cyclooxygenase-2 (prostaglandin-endoperoxide synthase 2, PTGS2) were evident in cells supplemented with ARA. For AHR and GSTM1 genes, significant repression of CYP1A1 was noted in PTS2A1 and PLA2G4A cells. Supplementation of HUVEC with ARA or EPA, and BaP resulted in a decrease in gene expression for VCAM-1(vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) adhesion molecules. EPA supplementation of endothelial cells resulted in the highest mRNA level for the NOS3 (nitric oxide synthase 3) gene. In HUVEC cells},
 abstract={incubated with EPA + LOVA + LPS or EPA + LOVA + TNF-α a significant decrease in mRNA levels for VCAM-1, PTGS1 (prostaglandin-endoperoxide synthase 1), PTGS2, and an increase in gene expression for NOS3 was noted. Repression of VCAM-1 and ICAM-1 adhesion molecules and PTGS1 and PTGS2 gene was observed following supplementation of HUVEC cells with EPA + LOVA and ARA + LOVA. The presented experiments' results indicate the anti-inflammatory, antioxidant and pro-resolving properties of eicosapentaenoic acid and an essential role in the modulation of these processes by n-6 fatty acids and lovastatin. Supplementation with polyunsaturated fatty acids seems to exert a therapeutic effect in inflamed endothelial cells.},
 title={The influence of n-3 and n-6 fatty acids on metabolic changes in inflamed endothelial cells},
 type={Praca doktorska},
 keywords={endothelial, n-3 and n-6 fatty acids, inflammation, pro-inflammatory genes and proteins expression},
}