Research Project
2880023
cis-Epoxyeicosatrienoic acid (EETs) are synthesized by arachidonic acid epoxygenases and hydrolyzed by epoxide hydrolases to vic- dihydroxyeicosatetraenoic acids (DHETs) in many tissues, including liver and kidney. EETs have potent vasoactive properties, stimulate peptide hormone release, and play a critical role in the adaptive response to a high salt-intake. Urinary excretion of EETs/DHETs increased during pregnancy-induced hypertension. EETs and DHETs, thus far, have been quantitated by gas chromatography/mass spectrometry (GC/MS), which is expensive and not suitable for clinical routines. Thus, the long-term objective of this project is to develop and market a comprehensive collection of enzyme-linked immunosorbent assays (ELISAs) for regioisomers of EETs and DHETs. In Phase I study, we will develop competitive ELISAs to quantitate 8,9-EET/DHET, and 14,15-EET/DHET. Following characterization of sensitivity and specificity of the ELISAs, the eicosanoids in biological systems will be quantitated and compared with those obtained by GC/MS. In Phase II study, we will develop ELISAs for remaining EETs and DHETs. Availability of ELISAs for EETs and DHETs will greatly facilitate study of biological activities of the epoxygenases and eicosanoids and lead to prevention and treatment of heart and kidney diseases.
