| First Author | Xiao J | Year | 2021 |
| Journal | J Biol Chem | Volume | 297 |
| Issue | 5 | Pages | 101315 |
| PubMed ID | 34678311 | Mgi Jnum | J:313334 |
| Mgi Id | MGI:6787322 | Doi | 10.1016/j.jbc.2021.101315 |
| Citation | Xiao J, et al. (2021) Intracellular receptor EPAC regulates von Willebrand factor secretion from endothelial cells in a PI3K/eNOS-dependent manner during inflammation. J Biol Chem :101315 |
| abstractText | Coagulopathy is associated with both inflammation and infection, including infection with novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. Clot formation is promoted via cyclic adenosine monophosphate (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-alpha (TNFalpha)-triggered vWF secretion from human umbilical vein endothelial cells (HUVECs) in a manner dependent upon inflammatory effector molecules phosphoinositide 3-kinase (PI3K) and endothelial nitric oxide synthase (eNOS). 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. |
