Ceramide enhances COX-2 expression and VSMC contractile hyperreactivity via ER stress signal activation
Ceramide enhances COX-2 expression and VSMC contractile hyperreactivity via ER stress signal activation
复制标题
神经酰胺通过 ER 应激信号激活增强 COX-2 表达和 VSMC 收缩高反应性
DOI：
10.1016/j.vph.2017.08.001
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发表时间：
2017-09-01
影响因子：
4
通讯作者：
Qian, Zongjie
中科院分区：
文献类型：
--
作者：
Zhang, Huina;Li, Juanfen;Qian, Zongjie
神经酰胺在血管中的蓄积已被归因于代谢性疾病中进行性血管并发症的血管功能障碍。本研究表明，神经酰胺预处理促进PE引起的大鼠内皮剥脱血管环的血管收缩在时间和剂量依赖性的方式。内质网（ER）应激抑制剂4-PBA和TUDCA、考克斯-2抑制剂塞来昔布和NS 398以及PGE（2）受体拮抗剂AH-6809可减弱神经酰胺促进的血管高反应性。神经酰胺可促进VSMCs中考克斯-2和BiP的转录和翻译表达，而ER应激抑制剂4-PBA和TUDCA可阻断这一作用。这些发现表明，神经酰胺通过介导ER应激/考克斯-2/PGE（2）途径增强PE诱导的血管平滑肌收缩。针对减少ER应激和考克斯-2激活的治疗策略可能有利于减轻血管并发症。化合物：C-2-神经酰胺（N-乙酰基-N-胆-鞘氨醇）CID：2662牛磺熊去氧胆酸钠（TUDCA）CID：9848818苯丙氨酸（PE）CID：6041。
Ceramide accumulation in blood vessels has been attributed to vascular dysfunction in progressive vascular complications in metabolic diseases. The present study showed that ceramide pretreatment promoted PE-induced vasoconstriction in rat endothelium-denuded vascular rings in a time- and dose-dependent manner. Endoplasmic reticulum (ER) stress inhibitors, 4-PBA and TUDCA, COX-2 inhibitors, Celecoxib and NS398, as well as PGE(2) receptor antagonist AH-6809 attenuated ceramide-promoted vascular hyperreactivity. Ceramide promoted the transcriptional and translational expression of COX-2 and BiP in VSMCs, which were blocked by the ER stress inhibitors, 4-PBA and TUDCA. These findings show that ceramide enhances PE-induced vascular smooth muscle constriction by mediation of the ER stress/COX-2/PGE(2) pathway. Therapeutic strategies targeted to reducing ER stress and COX-2 activation might be beneficial in attenuating vascular complications. Chemical compounds: C-2-Ceramide (N-acetyl-n-erythro-sphingosine) CID:2662Tauroursodeoxycholic Acid Sodium (TUDCA) CID:9848818phenylephrine (PE) CID:6041.