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Title: The assessment of eicosanoid profile in animal models of endothelial dysfunction


In this study, two original bioanalytical methods for quantification of eicosanoids biosynthesised from arachidonic acid (AA) via different metabolic pathways were developed and validated using UPLC-MS/MS technique. The methods allowed to assess the eicosanoid profile in selected animal models of endothelial dysfunction and its changes upon pharmacological modulation of vascular function.In NO-deficient mice, the biosynthesis of eicosanoids formed by cyclooxygenase (COX) was elevated. MNA treatment improved the vessel function by activation of COX-independent mechanisms.In murine model of hypertension, angiotensin II infusion increased the biosynthesis of CYP450- derived 20-HETE. The inhibition of thrombin activity by dabigatran improved the function of endothelium by sustaining the NO bioavailability and reducing the 20-HETE production.The development of 4T1 breast cancer was associated with the elevated biosynthesis of eicosanoids formed by COX and lipoxygenase (LOX) and with the reduced production of CYP450-derived AA metabolites. The inhibition of NO synthase increased the biosynthesis of epoxyeicosatrienoic acids (EET) and 20-HETE, which probably supported the disease progression under NO-deficiency.The obtained results show the heterogeneity of eicosanoid profile in investigated murine models of endothelial dysfunction and the pharmacological modulation of vascular function indicates which AA metabolic pathways could be an effective target in the treatment of hypertension and breast cancer.

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2 - studia doktoranckie

Degree grantor:

Uniwersytet Jagielloński. Collegium Medicum. Wydział Farmaceutyczny.


Maria Walczak ; Kamil Kuś

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tylko w bibliotece

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Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

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Last modified:

Oct 7, 2020

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Oct 7, 2020

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Edition name Date
ZB-131048 Oct 7, 2020


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