Cardiovascular therapeutic aspects of soluble epoxide hydrolase inhibitors. Cardiovasc Drug Rev 2006;24(2):169-88
Date
09/12/2006Pubmed ID
16961727DOI
10.1111/j.1527-3466.2006.00169.xScopus ID
2-s2.0-34247867952 (requires institutional sign-in at Scopus site) 86 CitationsAbstract
Soluble epoxide hydrolase (sEH) is an enzyme responsible for the conversion of lipid epoxides to diols by the addition of water. Biological actions on the cardiovascular system that are attributed to epoxides include vasodilation, antiinflammatory actions and vascular smooth muscle cell antimigratory actions. Conversion of arachidonic acid epoxides to diols by sEH diminishes the beneficial cardiovascular properties of these epoxyeicosano-ids. Cardiovascular diseases in animal models and humans have been associated with decreased epoxygenase activity or increased sEH activity and these changes are responsible for the progression of the disease state. More recently, sEH gene polymorphisms in the human population have been associated with increased risk for cardiovascular diseases. Thus the biological actions of epoxyeicosanoids and the sEH enzyme are ideal therapeutic targets for cardiovascular diseases. The rapid development of 1,3-disubstituted urea based sEH inhibitors over the past five years has resulted in a number of studies demonstrating cardiovascular protection. sEH inhibitors have antihypertensive and antiinflammatory actions and have been demonstrated to decrease cerebral ischemic and renal injury in rat models of hypertension. These findings of beneficial actions in animal models of disease position the sEH enzyme as a promising therapeutic target for cardiovascular diseases.
Author List
Imig JDMESH terms used to index this publication - Major topics in bold
AnimalsCardiotonic Agents
Cardiovascular Diseases
Enzyme Inhibitors
Epoxide Hydrolases
Humans
Models, Biological
Molecular Structure
Solubility
Vasodilation
