Differential Effects of sEH Inhibitors on the Proliferation and Migration of Vascular Smooth Muscle Cells.
Differential Effects of sEH Inhibitors on the Proliferation and Migration of Vascular Smooth Muscle Cells.
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DOI：
10.3390/ijms18122683
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发表时间：
2017-12-11
影响因子：
5.6
通讯作者：
Kang KW
中科院分区：
文献类型：
--
作者：
Kim HS;Kim SK;Kang KW
环氧二十碳三烯酸（EET）是花生四烯酸的心脏保护代谢产物。已知可溶性环氧化物水解酶（sEH）参与EET的代谢降解。血管平滑肌细胞（VSMCs）的异常增殖和迁移在动脉粥样硬化和再狭窄的发病机制中起重要作用。因此，本研究调查了sEH抑制剂12-（三环（3.3.1.13，7）癸-1-基氨基）羰基）氨基）-十二烷酸（AUDA）对血小板衍生生长因子（PDGF）诱导的大鼠VSMCs增殖和迁移的影响。AUDA显著抑制PDGF诱导的大鼠VSMC增殖，这与Pin 1抑制和血红素加氧酶-1（HO-1）上调相一致。然而，外源性8，9-EET、11，12-EET和14，15-EET处理不改变Pin 1或HO-1水平，对大鼠VSMCs增殖的影响很小。另一方面，AUDA增强PDGF刺激的大鼠VSMCs的细胞迁移。此外，AUDA诱导的环氧合酶-2（考克斯-2）活化和随后的血栓素A2（TXA 2）产生是增强迁移所必需的。此外，E2还可增加大鼠VSMCs的考克斯-2表达，但抑制其迁移。总之，本研究表明，AUDA对PDGF刺激的大鼠VSMCs的增殖和迁移产生不同的影响，这些结果可能不依赖于EET稳定。
Epoxyeicosatrienoic acid (EET) is a cardioprotective metabolite of arachidonic acid. It is known that soluble epoxide hydrolase (sEH) is involved in the metabolic degradation of EET. The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in the pathogenesis of atherosclerosis and restenosis. Thus, the present study investigated the effects of the sEH inhibitor 12-(((tricyclo(3.3.1.13,7)dec-1-ylamino)carbonyl)amino)-dodecanoic acid (AUDA) on platelet-derived growth factor (PDGF)-induced proliferation and migration in rat VSMCs. AUDA significantly inhibited PDGF-induced rat VSMC proliferation, which coincided with Pin1 suppression and heme oxygenase-1 (HO-1) upregulation. However, exogenous 8,9-EET, 11,12-EET, and 14,15-EET treatments did not alter Pin1 or HO-1 levels and had little effect on the proliferation of rat VSMCs. On the other hand, AUDA enhanced the PDGF-stimulated cell migration of rat VSMCs. Furthermore, AUDA-induced activation of cyclooxygenase-2 (COX-2) and subsequent thromboxane A2 (TXA2) production were required for the enhanced migration. Additionally, EETs increased COX-2 expression but inhibited the migration of rat VSMCs. In conclusion, the present study showed that AUDA exerted differential effects on the proliferation and migration of PDGF-stimulated rat VSMCs and that these results may not depend on EET stabilization.
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发表时间：
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