Preliminary data from studies in rodents suggests time-dependent associations between dietary LC n-3 PUFA and hepatic levels of the enzyme soluble epoxide hydrolase (sEH), which regulates the metabolism and availability of epoxyeicosatrienoic acids (EET). EET are cytochrome P450 epoxygenase products of arachidonic acid associated with lower blood pressure, decreased inflammatory response and inhibition of blood coagulation. To further investigate the association between LC n-3 PUFA and sEH, ApoE<sup>-</sup>/<sup>-</sup> mice were fed a high-fat high-cholesterol diet supplemented with either fish oil (EPA + DHA) or DHA or HOSF (all 2% w/w) for 10 weeks and livers and aortic roots were collected on day 2 and weeks 1, 2, 4 and 10. Proteomics analysis showed an overall decreasing effect of fish oil (but not DHA) supplementation on hepatic protein levels of sEH compared to the control throughout the intervention period (<i>P</i> < 0.05). Neither fish oil nor DHA intervention affected atherosclerotic plaque size in the aortic root. We also examined how dietary supplementation with 1 g/day EPA or 1 g/day DHA for 10 days affects platelet sEH levels and platelet aggregation compared to 1 g/day HOSF (control) in healthy volunteers in a double-blind, placebo-controlled, cross-over trial. We found that DHA decreased platelet aggregation by 10% (<i>P =</i> 0.04) and EPA also inhibited ADP (5 μM)-induced platelet aggregation by 14% compared to the control group but this effect did not reach statistical significance due to high variability between subjects. EPA decreased platelet sEH levels by 25% (not significant), whereas DHA had no effect. We also attempted to optimize a method for measuring EET in plasma and platelets. However, the rapid conversion of EET to other compounds and their low concentration in tissues prevented us from optimizing such a method within the time limits of the project.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:509187 |
| Date | January 2009 |
| Creators | Mavrommatis, Ioannis |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=56261 |
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