Effects of Inflammation and Soluble Epoxide Hydrolase Inhibition on Oxylipin Composition of Very Low‐Density Lipoproteins in Isolated Perfused Rat Livers

Effects of Inflammation and Soluble Epoxide Hydrolase Inhibition on Oxylipin Composition of Very Low‐Density Lipoproteins in Isolated Perfused Rat Livers

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Sheep Red Blood Cells Packed 100% from Innovative Research was used in the following study:

 

Effects of Inflammation and Soluble Epoxide Hydrolase Inhibition on Oxylipin Composition of Very Low‐Density Lipoproteins in Isolated Perfused Rat Livers

Rachel E. Walker, Olga V. Savinova, Theresa L. Pedersen, John W. Newman, Gregory C. Shearer

Physiological Reports
February 24, 2021

Oxylipins are metabolized from polyunsaturated fatty acids (PUFA) by enzymes of the lipoxygenase (LOX) and cytochrome P450 (CYP450) families and mediate cardiovascular health via modifying inflammation, thrombosis, hemostasis, and vascular tone. Although the oxylipin metabolites of arachidonic acid (AA) have been extensively studied, there is still more to learn about the metabolites of linoleic acid (LA), α‐linolenic acid (ALA), eicosapentaenoic acid (EPA), ω‐3 docosapentaenoic acid (DPA‐ω3), and docosahexaenoic acid (DHA). It has been observed that CYP450 epoxygenase metabolites produce epoxyeicosatrienoates (EpETrEs), a fatty acid with anti-hypertensive and anti-inflammatory properties.

Most oxylipins circulate in plasma lipoproteins for use or storage in peripheral tissues, as well as be directly taken into cells or bind to cell surface receptors. Very low‐density lipoproteins (VLDL) are the primary carriers of triglycerides and are synthesized in the liver, however it is unknown whether the liver directly regulates esterified oxylipin incorporation into the VLDL. VLDL’s role in inflammation could be explained by the presence of oxylipins, however there is evidence that oxylipins may undergo drastic changes under during and after disease states. Epoxides are of particular interest, as they are both anti-inflammatory and abundant in the VLDL. Due to their potential benefits, soluble epoxide hydrolase inhibitors (sEHi) have been investigated as a potential target for the treatment of a wide variety of diseases, specifically cardiovascular and chronic inflammatory diseases.

This study used a perfused liver model to observe the effect of inflammatory LPS and sEHi interactions on VLDL oxylipins. Their final observed VLDL-oxylipin concentrations with LPS and sEHi treatments did not correlate with linoleic acid kinetics, suggesting they were independently regulated under inflammatory conditions.

 

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  • Tags: Animal Blood Cells, Sheep Red Blood Cells Packed 100%

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