Soluble epoxide hydrolase: Sex differences and role in endothelial cell survival

Nandita C. Gupta, Catherine M. Davis, Jonathan W. Nelson, Jennifer M. Young, Nabil J. Alkayed

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Objective-Sex differences in cerebral ischemic injury are, in part, arrtibutable to the differences in cerebrovascular perfusion. We determined whether the brain microvascular endothelial cells (ECs) isolated from the female brain are more resistant to ischemic injury compared with male ECs, and whether the difference is attributable to lower expression of soluble epoxide hydrolase and higher levels of vasoprotective epoxyeicosatrienoic acids (EETs). We also determined whether protection by EETs is linked to the inhibition of rho-kinase (ROCK). Methods and Results-EC ischemic damage was measured after oxygen-glucose deprivation (OGD) using propidium iodide (PI) and cleaved caspase-3 labeling. Expression of soluble epoxide hydrolase was determined by quantitative polymerase chain reaction and immunocytochemistry, EETs levels by liquid chromatography-tandem mass spectrometry, and ROCK activity by ELISA. EC damage was higher in males compared with females, which correlated with higher soluble epoxide hydrolase mRNA, stronger immunoreactivity, and lower EETs compared with female ECs. Inhibition of soluble epoxide hydrolase abolished the sex difference in EC damage. ROCK activity was higher in male versus female ECs after OGD, and sex differences in EC damage and ROCK activity were abolished by 14,15-EET and ROCK inhibition. Conclusion-Sex differences in ischemic brain injury are, in part, attributable to differences in EET-mediated inhibition of EC ROCK activation after ischemia.

Original languageEnglish (US)
Pages (from-to)1936-1942
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume32
Issue number8
DOIs
StatePublished - Aug 1 2012

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Keywords

  • endothelial cell
  • epoxyeicosatrienoic acids
  • oxygen-glucose deprivation
  • rho-kinase
  • soluble epoxide hydrolase

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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