Intracellular receptor EPAC regulates von Willebrand factor secretion from endothelial cells in a PI3K-/eNOS-dependent manner during inflammation.
Intracellular receptor EPAC regulates von Willebrand factor secretion from endothelial cells in a PI3K-/eNOS-dependent manner during inflammation.
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DOI：
10.1016/j.jbc.2021.101315
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Gong B
中科院分区：
文献类型：
--
作者：
Xiao J;Zhang B;Su Z;Liu Y;Shelite TR;Chang Q;Qiu Y;Bei J;Wang P;Bukreyev A;Soong L;Jin Y;Ksiazek T;Gaitas A;Rossi SL;Zhou J;Laposata M;Saito TB;Gong B
凝血病与炎症和感染相关，包括新型严重急性呼吸综合征冠状病毒2型感染，其病原体凝血病与炎症和感染相关，包括新型严重急性呼吸综合征冠状病毒2型感染，其病原体为COVID-19。通过cAMP介导的血管性血友病因子（vWF）分泌促进凝块形成，vWF可微调止血过程。由cAMP直接激活的交换蛋白（EPAC）是一种广泛表达的细胞内cAMP受体，在抑制炎症中起调节作用。为了评估EPAC是否可以调节炎症过程中vWF的释放，我们利用了我们的EPAC 1基因缺失小鼠模型，并发现在EPAC 1基因缺失的情况下，内毒素血症小鼠中vWF的分泌增加。体外EPAC 1的药理学抑制模拟EPAC 1-/-表型。此外，EPAC 1以依赖于炎症效应分子PI 3 K和内皮型一氧化氮合酶的方式调节肿瘤坏死因子-α触发的人脐静脉内皮细胞vWF分泌。此外，在体内和体外，EPAC 1激活减少炎症触发的vWF释放。我们的数据描述了EPAC 1在vWF分泌中的一种新的调节作用，并揭示了在炎症过程中控制血栓形成的新策略的潜在发展。
Coagulopathy is associated with both inflammation and infection, including infections with novel severe acute respiratory syndrome coronavirus-2, the causative agent Coagulopathy is associated with both inflammation and infection, including infection with novel severe acute respiratory syndrome coronavirus-2, the causative agent of COVID-19. Clot formation is promoted via cAMP-mediated secretion of von Willebrand factor (vWF), which fine-tunes the process of hemostasis. The exchange protein directly activated by cAMP (EPAC) is a ubiquitously expressed intracellular cAMP receptor that plays a regulatory role in suppressing inflammation. To assess whether EPAC could regulate vWF release during inflammation, we utilized our EPAC1-null mouse model and revealed increased secretion of vWF in endotoxemic mice in the absence of the EPAC1 gene. Pharmacological inhibition of EPAC1 in vitro mimicked the EPAC1-/- phenotype. In addition, EPAC1 regulated tumor necrosis factor-α–triggered vWF secretion from human umbilical vein endothelial cells in a manner dependent upon inflammatory effector molecules PI3K and endothelial nitric oxide synthase. Furthermore, EPAC1 activation reduced inflammation-triggered vWF release, both in vivo and in vitro. Our data delineate a novel regulatory role for EPAC1 in vWF secretion and shed light on the potential development of new strategies to control thrombosis during inflammation.
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影响因子：
3.8
作者：
Gong B;Ma L;Liu Y;Gong Q;Shelite T;Bouyer D;Boor PJ;Lee YS;Oberhauser A
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影响因子：
20.3
作者：
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DOI：
10.3791/3564
发表时间：
2012-07-30
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
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通讯作者：
Shain, William