Cardiovascular therapeutic aspects of soluble epoxide hydrolase inhibitors

被引:79
作者
Imig, John D. [1 ]
机构
[1] Med Coll Georgia, Vasc Biol Ctr, Dept Physiol, Augusta, GA 30912 USA
来源
CARDIOVASCULAR DRUG REVIEWS | 2006年 / 24卷 / 02期
关键词
CYP450; metabolites; epoxide hydrolase; epoxyeicosatrienoic acids; hypertension; inflammation; nephropathy; stroke;
D O I
10.1111/j.1527-3466.2006.00169.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 epoxyeicosanoids. 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.
引用
收藏
页码:169 / 188
页数:20
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