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:2662 Tauroursodeoxycholic Acid Sodium (TUDCA) CID:9848818 phenylephrine (PE) CID:6041.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81471082, 81670794, 81470567]; Guangxi Science and Technology Research Project for University [YB201483]; Research and Development Project of Medical and Health appropriate Technology of Guangxi [S201407-02]
第一作者机构：[1]Capital Med Univ, Beijing An Zhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Key Lab Upper Airway Dysfunct Related Cardiovasc, Beijing, Peoples R China;
通讯作者：
通讯机构：[1]Capital Med Univ, Beijing An Zhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Key Lab Upper Airway Dysfunct Related Cardiovasc, Beijing, Peoples R China;[2]Guilin Med Univ, Affiliated Hosp, Dept Cardiovasc Med, Guilin, Guangxi, Peoples R China;
推荐引用方式(GB/T 7714)：
Zhang Huina,Li Juanfen,Li Linghai,et al.Ceramide enhances COX-2 expression and VSMC contractile hyperreactivity via ER stress signal activation[J].VASCULAR PHARMACOLOGY.2017,96-98:26-32.doi:10.1016/j.vph.2017.08.001.
APA：
Zhang, Huina,Li, Juanfen,Li, Linghai,Liu, Pingsheng,Wei, Yongxiang&Qian, Zongjie.(2017).Ceramide enhances COX-2 expression and VSMC contractile hyperreactivity via ER stress signal activation.VASCULAR PHARMACOLOGY,96-98,
MLA：
Zhang, Huina,et al."Ceramide enhances COX-2 expression and VSMC contractile hyperreactivity via ER stress signal activation".VASCULAR PHARMACOLOGY 96-98.(2017):26-32
