Evidence map›Paper›PMID 38203706›Full record

ArticleInternational journal of molecular sciences2023

Depletion of Endothelial-Derived 2-AG Reduces Blood-Endothelial Barrier Integrity via Alteration of VE-Cadherin and the Phospho-Proteome.

Aidan A Levine, Erika Liktor-Busa, Shreya Balasubramanian, Seph M Palomino, Anya M Burtman, Sarah A Couture, Austin A Lipinski, Paul R Langlais, Tally M Largent-Milnes

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 25% 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

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 5 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Aidan A LevineDepartment of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Erika Liktor-BusaDepartment of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Shreya BalasubramanianDepartment of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Seph M PalominoDepartment of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Anya M BurtmanDepartment of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Sarah A CoutureDepartment of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Austin A LipinskiDivision of Endocrinology, Department of Medicine, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Paul R LanglaisDivision of Endocrinology, Department of Medicine, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.ORCID 0000-0003-1929-737X
Tally M Largent-MilnesDepartment of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.ORCID 0000-0001-7599-102X
University of Arizona · US

Funding

VITAMIN AP30CA023074 · NCI · UNIVERSITY OF ARIZONA · PI Jennifer Wright Bea · 1985 to 2026
$110.2M
The Center of Excellence in Addiction Studies (CEAS)P30DA051355 · NIDA · UNIVERSITY OF ARIZONA · PI PORRECA, FRANK, VANDERAH, TODD W · 2021 to 2025
$6.7M
Targeting the Endocannabinoid System for Headache InterventionR01NS126752 · NINDS · UNIVERSITY OF ARIZONA · PI Tally Marie Milnes · 2023 to 2026
$2.4M
Blood Brain Barrier and Migraine: Effect on Therapy (Diversity Supplement)R01NS099292 · NINDS · UNIVERSITY OF ARIZONA · PI MILNES, TALLY MARIE · 2017 to 2021
$1.7M
Primary Afferent Transmission in the Trigeminal Dorsal HornF32DE022499 · NIDCR · OREGON HEALTH & SCIENCE UNIVERSITY · PI MILNES, TALLY MARIE · 2011 to 2014
$127k
NCI NIH HHS P30 CA023074NCI NIH HHS P30CA023074NIDA NIH HHS P30 DA051355NIDA NIH HHS P30DA051355NIDCR NIH HHS F32 DE022499NINDS NIH HHS R01 NS099292NINDS NIH HHS R01NS099292NINDS NIH HHS R01 NS126752NINDS NIH HHS R01NS126752-01A1
6 · The paper itself

Abstract

Mounting evidence supports the role of the endocannabinoid system in neurophysiology, including blood-brain barrier (BBB) function. Recent work has demonstrated that activation of endocannabinoid receptors can mitigate insults to the BBB during neurological disorders like traumatic brain injury, cortical spreading depression, and stroke. As alterations to the BBB are associated with worsening clinical outcomes in these conditions, studies herein sought to examine the impact of endocannabinoid depletion on BBB integrity. Barrier integrity was investigated in vitro via bEnd.3 cell monolayers to assess endocannabinoid synthesis, barrier function, calcium influx, junctional protein expression, and proteome-wide changes. Inhibition of 2-AG synthesis using DAGLα inhibition and siRNA inhibition of DAGLα led to loss of barrier integrity via altered expression of VE-cadherin, which could be partially rescued by exogenous application of 2-AG. Moreover, the deleterious effects of DAGLα inhibition on BBB integrity showed both calcium and PKC (protein kinase C)-dependency. These data indicate that disruption of 2-AG homeostasis in brain endothelial cells, in the absence of insult, is sufficient to disrupt BBB integrity thus supporting the role of the endocannabinoid system in neurovascular disorders.

Indexed as

Antigens, CDCadherinsEndothelial CellsProteomeCadherin 5CalciumCalcium, DietaryEndocannabinoidsAntigens, CDCadherin 5CadherinsCalciumCalcium, DietaryEndocannabinoidsProteome2-AGblood–brain barrierDAGLαendocannabinoidVE-cadherin

Identifiers

PMID38203706
PMCPMC10778805
OpenAlexW4390470951

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.