Evidence map›Paper›PMID 34678311›Full record

ArticleThe Journal of biological chemistry2021

Intracellular receptor EPAC regulates von Willebrand factor secretion from endothelial cells in a PI3K-/eNOS-dependent manner during inflammation.

Jie Xiao, Ben Zhang, Zhengchen Su, Yakun Liu, Thomas R Shelite, Qing Chang, Yuan Qiu, Jiani Bei, Pingyuan Wang, Alexander Bukreyev and 9 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.3field-weighted citation impact, top 39% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Article
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  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 3 institutions in 1 country.

Jie XiaoDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Ben ZhangDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Zhengchen SuDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Yakun LiuDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Thomas R SheliteDepartment of Internal Medicine, Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA.
Qing ChangDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Yuan QiuDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Jiani BeiDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Pingyuan WangDepartment of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, USA.
Alexander BukreyevDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Lynn SoongDepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.
Yang JinDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Boston University Medical Campus, Boston, Massachusetts, USA.
Thomas KsiazekDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Angelo GaitasThe Estelle and Daniel Maggin Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Shannan L RossiDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Jia ZhouDepartment of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, USA.
Michael LaposataDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Tais B SaitoDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Bin GongDepartment of Pathology, University of Texas Medical Branch, Galveston, Texas, USA. Electronic address: bigong@utmb.edu.
The University of Texas Medical Branch at Galveston · USBoston University · USIcahn School of Medicine at Mount Sinai · US

Funding

Pathogenic Mechanisms of Vascular Dysfunction in Scrub TyphusR01AI132674 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI Yuejin Liang, LYNN SOONG · 2018 to 2026
$3.0M
Epac1 Plays a Critical Role in Bacterial Adhesion during RickettsiosesR01AI121012 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI GONG, BIN · 2016 to 2020
$1.9M
Targeting the Host Adenosine A2A Receptor to Protect Against Fatal Rickettsiosis Using an Approved Parkinson's Disease DrugR21AI137785 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI GONG, BIN · 2018 to 2019
$440k
The role of IL-1 family of cytokines in tick-transmitted ehrlichiosisR21AI144328 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI GONG, BIN · 2019 to 2020
$435k
Targeting extracellular tRNA-derived RNA fragments (tRFs) to protect against fatal rickettsiosisR21AI154211 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI GONG, BIN · 2020 to 2021
$435k
Inflammasome activation and ehrlichial dissemination in tick vs needle transmissionR03AI142406 · NIAID · UNIVERSITY OF TEXAS MED BR GALVESTON · PI GONG, BIN · 2019 to 2020
$158k
NIAID NIH HHS R01 AI121012NIAID NIH HHS R01 AI132674NIAID NIH HHS R03 AI142406NIAID NIH HHS R21 AI137785NIAID NIH HHS R21 AI144328NIAID NIH HHS R21 AI154211
6 · The paper itself

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.

Indexed as

AnimalsCOVID-19Disease Models, AnimalEndothelial CellsGuanine Nucleotide Exchange FactorsInflammationMiceMice, KnockoutNitric Oxide Synthase Type IIIPhosphatidylinositol 3-Kinasesvon Willebrand FactorEpac protein, mouseGuanine Nucleotide Exchange FactorsNitric Oxide Synthase Type IIINos3 protein, mousePhosphatidylinositol 3-Kinasesvon Willebrand FactorAFMendothelial celleNOSEPACinflammationPI3Kspatial proximityvon Willebrand factor secretionWeibel–Palade body

Identifiers

PMID34678311
PMCPMC8526113
OpenAlexW3205955068

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.