Abstract
Epoxyeicosatrienoic acids (EETs) are epoxy fatty acids that have biological actions that are essential for maintaining water and electrolyte homeostasis. An inability to increase EETs in response to a high-salt diet results in salt-sensitive hypertension. Vasodilation, inhibition of epithelial sodium channel, and inhibition of inflammation are the major EET actions that are beneficial to the heart, resistance arteries, and kidneys. Genetic and pharmacological means to elevate EETs demonstrated antihypertensive, anti-inflammatory, and organ protective actions. Therapeutic approaches to increase EETs were then developed for cardiovascular diseases. sEH (soluble epoxide hydrolase) inhibitors were developed and progressed to clinical trials for hypertension, diabetes mellitus, and other diseases. EET analogs were another therapeutic approach taken and these drugs are entering the early phases of clinical development. Even with the promise for these therapeutic approaches, there are still several challenges, unexplored areas, and opportunities for epoxy fatty acids.
Highlights
Abstract —Epoxyeicosatrienoic acids (EETs) are epoxy fatty acids that have biological actions that are essential for maintaining water and electrolyte homeostasis
The decrease in blood pressure in response to sEH inhibitors or genetic EPHX2 deletion was associated with an increase in the epoxyeicosatrienoic acids (EETs) to DHET ratio, natriuresis, improved renal microvascular function, and decreased renal inflammation.[53]
We found that primary renal endothelial cells isolated from Tie2-CYP2J2 and Tie2CYP2C8 mice produced significantly higher concentrations of 11,12-EET and 14,15-EET compared with renal endothelial cells isolated from wild-type controls.[115]
Summary
Abstract —Epoxyeicosatrienoic acids (EETs) are epoxy fatty acids that have biological actions that are essential for maintaining water and electrolyte homeostasis.
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