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Enzymatic Synthesis of Epoxidized Metabolites of Docosahexaenoic, Eicosapentaenoic, and Arachidonic Acids

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Aging, estrogen loss and epoxyeicosatrienoic acids (EETs).

Alison R Lee¹, Angela S Pechenino, Hua Dong

¹Molecular & Cellular Cardiology, Cardiovascular Division, Department of Medicine, University of California Davis, Davis, California, USA.

|August 23, 2013

Summary

Aging and estrogen loss do not decrease anti-inflammatory epoxyeicosatrienoic acids (EETs) in the cardiovascular system. This study investigated the impact of aging and estrogen deficiency on EETs levels in rats.

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Area of Science:

Cardiovascular Science
Endocrinology
Metabolism

Background:

Inflammation is central to cardiovascular diseases, exacerbated by menopause-induced estrogen loss and aging.
Epoxyeicosatrienoic acids (EETs) are anti-inflammatory compounds derived from arachidonic acid via cytochrome P450 (Cyp) enzymes.
Estrogen loss and aging are hypothesized to reduce anti-inflammatory EETs.

Purpose of the Study:

To investigate the effects of aging and estrogen loss on the levels of anti-inflammatory EETs in a rat model.
To determine if estrogen replacement therapy influences EETs levels in aged and adult rats.

Main Methods:

Adult and aged ovariectomized rats, with and without estrogen replacement, were utilized.
Mass spectrometry quantified EETs and their metabolites (DHETs).
Western blotting assessed levels of key Cyp enzymes and soluble epoxide hydrolase (sEH).

Main Results:

Overall Cyp levels decreased with age, with a notable increase in liver Cyp2C6.
Soluble epoxide hydrolase (sEH) increased in the kidney with estrogen replacement.
No significant changes in plasma or aortic EETs levels were observed, though specific DHET metabolites showed altered levels.

Conclusions:

Neither aging nor estrogen loss led to a decrease in anti-inflammatory EETs within the cardiovascular system.
The findings challenge the initial hypothesis regarding reduced EETs due to aging and estrogen deficiency.
Further research may be needed to understand the complex regulation of EETs metabolism in cardiovascular health.