Soluble epoxide hydrolase as a therapeutic target for cardiovascular diseases.
The cardiovascular effects of epoxyeicosatrienoic acids (EETs) include vasodilation, antimigratory actions on vascular smooth muscle cells and anti-inflammatory actions. These endogenous lipid mediators are broken down into diols by soluble epoxide hydrolase (sEH), and so inhibiting this enzyme would be expected to enhance the beneficial cardiovascular properties of EETs. sEH inhibitors (sEHIs) that are based on 1,3-disubstituted urea have been rapidly developed, and have been shown to be antihypertensive and anti-inflammatory, and to protect the brain, heart and kidney from damage. Although challenges for the future exist - including improving the drug-like properties of sEHIs and finding better ways to target sEHIs to specific tissues - the recent initiation of the first clinical trials of sEHIs has highlighted the therapeutic potential of these agents.
Imig
John D
JD
Department of Pharmacology and Toxicology, Cardiovascular Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA. jdimig@mcw.edu
Hammock
Bruce D
BD
D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000201:enzymology*; D016503:Drug Delivery Systems / Q000379:methods*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D004851:Epoxide Hydrolases