Bruce Hammock, Ph.D.
University of California, Davis
NIEHS grantees discovered that estrogen can block the function of soluble epoxide hydrolase (sEH), an enzyme in cells that degrades chemically stable fatty acid metabolites. Because inhibition of sEH can be cardioprotective, this finding may help explain why women generally have a lower incidence of cardiovascular disease than men.
Using mice and human cells, the researchers showed that estrogen is responsible for DNA methylation of the gene Ephx2, which blocks the gene’s ability to promote sEH expression. This sEH inhibition can raise levels of epoxyeicosatrienoic acids (EETs), which are omega-6 fatty acid metabolites that are generally degraded by sEH. Because EETs are cardioprotective and can lower blood pressure, increases in EETs caused by estrogen suppression of sEH can help protect against heart disease.
According to the authors, this finding also highlights the potential for using sEH inhibitors that share the same target with estrogen to prevent negative cardiovascular outcomes that may result from estrogen deficiency.
Citation: Yang YM, Sun D, Kandhi S, Froogh G, Zhuge J, Huang W, Hammock BD4, Huang A. 2018. Estrogen-dependent epigenetic regulation of soluble epoxide hydrolase via DNA methylation. Proc Natl Acad Sci U S A 115(3):613–618.