Soluble epoxide hydrolase inhibitors and heart failure.
Soluble epoxide hydrolase inhibitors and heart failure.
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DOI：
10.1111/j.1755-5922.2010.00150.x
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发表时间：
2011-04
影响因子：
3.1
通讯作者：
Chiamvimonvat N
中科院分区：
文献类型：
--
作者：
Qiu H;Li N;Liu JY;Harris TR;Hammock BD;Chiamvimonvat N
心血管疾病仍然是西方社会死亡的主要原因之一。心力衰竭（HF）主要是由于伴随心肌重构的进行性心肌功能障碍。一旦发生心力衰竭，在大多数情况下，这种情况是不可逆转的，并且死亡率很高。可溶性环氧化物水解酶 (sEH) 是一种催化环氧二十碳三烯酸 (EET) 水解的酶，EET 是通过细胞色素 P450 环氧化酶途径衍生自花生四烯酸的脂质介质。 EET 已被证明具有血管舒张、抗炎和心脏保护作用。当 EET 被 sEH 水解成相应的二羟基二十碳三烯酸 (DHET) 时，它们的心脏保护活性变得不那么明显。最近的基因研究已确定 sEH 是心力衰竭的易感基因，与此一致，sEH 酶作为心血管疾病的有吸引力的治疗靶点受到了相当多的关注。事实上，sEH 抑制已被证明具有抗高血压和抗炎作用，这可能是由于内源性 EET 和其他环氧脂的生物利用度增加，并且已经开发出几种有效的 sEH 抑制剂，并在心血管疾病（包括高血压、心脏肥大和缺血/再灌注损伤）的动物模型中进行了测试。 sEH抑制剂治疗已被证明可以有效预防压力超负荷和血管紧张素II诱导的心脏肥大，并逆转由慢性压力超负荷引起的预先形成的心脏肥大。 sEH 抑制剂在几种心脏缺血/再灌注损伤模型中的应用减少了梗塞面积并阻止了进行性心脏重塑。此外，sEH抑制剂的使用可以防止与心脏肥大和缺血/再灌注损伤相关的电重构和室性心律失常的发生。迄今为止发表的数据支持这样的观点，即 sEH 抑制剂可能代表一种有前途的治疗方法，用于对抗有害的心脏重塑和心力衰竭。
Cardiovascular disease remains one of the leading causes of death in the Western societies. Heart failure (HF) is due primarily to progressive myocardial dysfunction accompanied by myocardial remodeling. Once heart failure develops, the condition is, in most cases, irreversible and is associated with a very high mortality rate. Soluble epoxide hydrolase (sEH) is an enzyme that catalyzes the hydrolysis of epoxyeicosatrienoic acids (EETs), which are lipid mediators derived from arachidonic acid through the cytochrome P450 epoxygenase pathway. EETs have been shown to have vasodilatory, anti-inflammatory and cardioprotective effects. When EETs are hydrolyzed by sEH to corresponding dihydroxyeicosatrienoic acids (DHETs), their cardioprotective activities become less pronounced. In line with the recent genetic study that has identified sEH as a susceptibility gene for heart failure, the sEH enzyme has received considerable attention as an attractive therapeutic target for cardiovascular diseases. Indeed, sEH inhibition has been demonstrated to have anti-hypertensive and anti-inflammatory actions, presumably due to the increased bioavailability of endogenous EETs and other epoxylipids, and several potent sEH inhibitors have been developed and tested in animal models of cardiovascular disease including hypertension, cardiac hypertrophy and ischemia/reperfusion injury. sEH inhibitor treatment has been shown to effectively prevent pressure overload- and angiotensin II-induced cardiac hypertrophy and reverse the pre-established cardiac hypertrophy caused by chronic pressure overload. Application of sEH inhibitors in several cardiac ischemia/reperfusion injury models reduced infarct size and prevented the progressive cardiac remodeling. Moreover, the use of sEH inhibitors prevented the development of electrical remodeling and ventricular arrhythmias associated with cardiac hypertrophy and ischemia/reperfusion injury. The data published to date support the notion that sEH inhibitors may represent a promising therapeutic approach for combating detrimental cardiac remodeling and heart failure.
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发表时间：
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影响因子：
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作者：
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影响因子：
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