Your browser doesn't support javascript.
Intracellular receptor EPAC regulates von Willebrand factor secretion from endothelial cells in a PI3K-/eNOS-dependent manner during inflammation.
Xiao, Jie; Zhang, Ben; Su, Zhengchen; Liu, Yakun; Shelite, Thomas R; Chang, Qing; Qiu, Yuan; Bei, Jiani; Wang, Pingyuan; Bukreyev, Alexander; Soong, Lynn; Jin, Yang; Ksiazek, Thomas; Gaitas, Angelo; Rossi, Shannan L; Zhou, Jia; Laposata, Michael; Saito, Tais B; Gong, Bin.
  • Xiao J; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Zhang B; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Su Z; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Liu Y; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Shelite TR; Department of Internal Medicine, Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA.
  • Chang Q; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Qiu Y; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Bei J; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Wang P; Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Bukreyev A; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Soong L; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Jin Y; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University Medical Campus, Boston, Massachusetts, USA.
  • Ksiazek T; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Gaitas A; The Estelle and Daniel Maggin Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
  • Rossi SL; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Zhou J; Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Laposata M; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Saito TB; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
  • Gong B; Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA. Electronic address: bigong@utmb.edu.
J Biol Chem ; 297(5): 101315, 2021 11.
Article in English | MEDLINE | ID: covidwho-1472025
ABSTRACT
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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Von Willebrand Factor / Phosphatidylinositol 3-Kinases / Guanine Nucleotide Exchange Factors / Endothelial Cells / Nitric Oxide Synthase Type III Limits: Animals Language: English Journal: J Biol Chem Year: 2021 Document Type: Article Affiliation country: J.jbc.2021.101315

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Von Willebrand Factor / Phosphatidylinositol 3-Kinases / Guanine Nucleotide Exchange Factors / Endothelial Cells / Nitric Oxide Synthase Type III Limits: Animals Language: English Journal: J Biol Chem Year: 2021 Document Type: Article Affiliation country: J.jbc.2021.101315