Title:Diabetic CVD – Soluble Epoxide Hydrolase as A Target
Volume: 10
Issue: 3
Author(s): Aurelien Lorthioir, Dominique Guerrot, Robinson Joannides and Jeremy Bellien
Affiliation:
Keywords:
Antihypertensive agent, cardiovascular diseases, cytochrome P450 epoxygenase, diabetes, endothelium,
epoxyeicosatrienoic acids, insulin release, insulin resistance, soluble epoxide hydrolase, vasodilatation
Abstract: The incidence of cardiovascular diseases remains high in diabetic patients despite the optimization of blood
glucose control and the therapeutic management of risk factors. One emerging promising pharmacological approach that
may help to prevent the development of diabetic cardiovascular complications is to improve endothelial function through
the restoration of the bioavailability of epoxyeicosatrienoic acids (EETs). EETs are crucial eicosanoid signaling molecules
synthesized by cytochrome P450 epoxygenases in the vascular endothelium and in pancreatic islets. EETs promote
vasodilatation and display attractive anti-inflammatory and anti-aggregating actions together with potent effects on insulin
release and sensitivity. In animal models of insulin-resistance and diabetes, a decrease in EET availability has been
reported, and is a deleterious mechanism that probably contributes to multiple metabolic, cardiovascular and renal
disorders in this setting. Moreover, increasing experimental evidence suggest that the use of soluble epoxide hydrolase
(sEH) inhibitors, which prevent EET degradation, is a promising pharmacological approach to prevent endothelial
dysfunction and to protect against target organ damage in metabolic diseases. This review presents evidence that the EET
pathway is disturbed from the early stages of metabolic diseases, and analyzes the potential contribution of EETs
impairment to the progression of cardiovascular diseases associated with diabetes. Pathophysiological and therapeutic
perspectives are thereafter discussed, including the necessity to demonstrate the role of EET pathway alterations in
endothelial dysfunction associated with diabetes in human, and the interest of sEH inhibitors to prevent the development
of diabetic cardiovascular complications, with the expected result of improving patients' health.
