his increase in Cyp2C6 was mirrored in the kidney. EET purchase Neuromedin N levels are determined not just by production via the Cyp’s, but also by metabolism to DHETs by sEH. Aging had no effect on sEH levels in the liver or kidney; estrogen replacement, however, lead to increased levels of sEH compared to Adult Ovx, as expected from murine studies. Predicting how plasma levels of EETs should vary based on protein expression is complicated by this variation in Cyp and sEH levels. However, the measured plasma levels showed no significant differences in any of the four isomers with either aging or estrogen status. It seems reasonable that there is no change in total EETs given the various increases and decreases in protein levels. 8913470 It is interesting however, that there is no significant change in the distribution of EET isomers to go along with these changes, given that the different Cyp enzymes can form all of the isomers, but have some level of selectivity. Given that EETs levels do not vary significantly with age or estrogen status, levels of DHETs should largely be dependent principally upon sEH metabolism of the corresponding EETs. The only differences seen were an increase in 14,15 DHET in aged ovx and an increase in 5,6 DHET in adult OP. The only groups with increased sEH expression were adult and aged OP. The oxylipins 8540743 measured are free fatty acid oxylipins which have been widely used as biomarkers of biologically active fatty acid chemical mediators. Given that over 90% of the plasma EETs was esterified to the phospholipids of circulating lipoproteins, it is expected that the downstream effect of these plasma metabolites will be influenced by shifts in lipoprotein metabolism. The plasma oxylipin levels may not reflect the levels of oxylipins in different tissues, in different plasma fractions, or the oxylipins sequestered as phospholipids and other esters; however, free EETs are thought to be the major biologically active form, with phospholipid EETs being a storage or inactive form. There is little information concerning whether the EETs and other eicosanoids in the phospholipids represent the major pools and generally what conditions mobilize the EETs. In multiple previous studies, the correlation of plasma lipid mediators with biologic activities has proven accurate. Plasma EETs levels – were generally highest in the aged ovx, but this did not reach significance. In contrast, 14,15 DHET levels were clearly increased in aged ovx. Our average values for the various EET isoforms among the groups was 28 nM. This is not inconsistent with other groups, however published values vary significantly. Reported levels of 14,15 EET range from 0.3 to 13 nM, and 11,12 EET from 0.3 to 48.5 nM . Partly, this is due to differences in methodology. It can be challenging to compare levels between and among papers, because measurements often differ, for example measuring total EETs, versus just 11,12 EET, or 14,15 EET. In addition, nearly all previous studies examined only juvenile or young adult models. With an interest in EETs as a possible therapeutic for decreasing inflammation, we looked also at Cyp expression in the heart and vasculature. In the heart, Cyp 2C6 was decreased in both aged groups. Cyp 2C2 was decreased in the Aged OP group, while Cyp 2J2 was unchanged. Neither aging nor estrogen status effected sEH. The changes in Cyp and sEH protein expression are similar to that in the liver. Polymorphisms in Cyp2J2 are associated with increased risk of coronary a
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