RT Journal Article
SR Electronic
T1 The Pharmacology of the Cytochrome P450 Epoxygenase/Soluble Epoxide Hydrolase Axis in the Vasculature and Cardiovascular Disease
JF Pharmacological Reviews
JO Pharmacol Rev
FD American Society for Pharmacology and Experimental Therapeutics
SP 1106
OP 1140
DO 10.1124/pr.113.007781
VO 66
IS 4
A1 Ingrid Fleming
A2 Ulf Simonsen
YR 2014
UL http://pharmrev.aspetjournals.org/content/66/4/1106.abstract
AB Over the last 20 years, it has become clear that cytochrome P450 (P450) enzymes generate a spectrum of bioactive lipid mediators from endogenous substrates. However, studies focused on the determining biologic activity of the P450 system have focused largely on the metabolites generated by one substrate (i.e., arachidonic acid). However, epoxides and diols derived from other endogenous substrates, such as linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid, may be generated in higher concentrations and may potentially be of more physiologic relevance. Recent studies that used a combination of phenotyping and lipid array analyses revealed that rather than being inactive products, fatty acid diols play important roles in a number of biologic processes including inflammation, angiogenesis, and metabolic regulation. Moreover, inhibitors of the soluble epoxide hydrolase that increase epoxide but decrease diol levels have potential for the treatment of the metabolic syndrome.