Evidence map›Paper›PMID 25845662›Full record

ArticleDiabetes2015

M2 Macrophage Polarization Mediates Anti-inflammatory Effects of Endothelial Nitric Oxide Signaling.

Woo Je Lee, Sanshiro Tateya, Andrew M Cheng, Norma Rizzo-DeLeon, Nicholas F Wang, Priya Handa, Carole L Wilson, Alexander W Clowes, Ian R Sweet, Karol Bomsztyk and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% 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

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.

  1. Pooled it
  2. TPx Protein ofPathogens (Basel, Switzerland) · 2026
    Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. PKCδ regulates the vascular biology in diabetic atherosclerosis.Cell communication and signaling : CCS · 2023
    Review
  15. Article
  16. Review
  17. Utility of NO and HNitric oxide : biology and chemistry · 2022
    Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Woo Je LeeDepartment of Medicine, University of Washington, Seattle, WA Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA.
Sanshiro TateyaDepartment of Medicine, University of Washington, Seattle, WA Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA.
Andrew M ChengDepartment of Medicine, University of Washington, Seattle, WA Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA.
Norma Rizzo-DeLeonDepartment of Medicine, University of Washington, Seattle, WA Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA.
Nicholas F WangDepartment of Medicine, University of Washington, Seattle, WA Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA.
Priya HandaDepartment of Medicine, University of Washington, Seattle, WA Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA.
Carole L WilsonDepartment of Pathology, University of Washington, Seattle, WA.
Alexander W ClowesDepartment of Surgery, University of Washington, Seattle, WA.
Ian R SweetDepartment of Medicine, University of Washington, Seattle, WA Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA.
Karol BomsztykDepartment of Medicine, University of Washington, Seattle, WA.
Michael W SchwartzDepartment of Medicine, University of Washington, Seattle, WA Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA.
Francis KimDepartment of Medicine, University of Washington, Seattle, WA Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA fkim@u.washington.edu.
University of Washington · US

Funding

Coordinating and Bioinformatics Unit for the MMPC/DiaCompU24DK076169 · NIDDK · AUGUSTA UNIVERSITY · PI MCINDOE, RICHARD A. · 2006 to 2018
$42.4M
Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · PI Karin E Bornfeldt · 1986 to 2026
$41.4M
PILOT STUDY--CLINICAL NUTRITION RESEARCHP30DK035816 · NIDDK · UNIVERSITY OF WASHINGTON · PI Ellen A Schur · 1986 to 2026
$30.4M
CARDIOVASCULAR RESEARCH TRAINING PROGRAMT32HL007828 · NHLBI · UNIVERSITY OF WASHINGTON · PI Francis Kim, Farid Moussavi-Harami · 1997 to 2026
$10.2M
Novel Brain Mechanisms Controlling Glucose HomeostasisR01DK083042 · NIDDK · UNIVERSITY OF WASHINGTON · PI SCHWARTZ, MICHAEL W · 2008 to 2025
$7.6M
Integration of Long- and Short-Term Control of FeedingP01DK068384 · NIDDK · UNIVERSITY OF WASHINGTON · PI SCHWARTZ, MICHAEL W · 2004 to 2010
$6.1M
ATHEROSCLEROTIC PLAQUE PROGRESSION AND THROMBOSISR37HL052459 · NHLBI · UNIVERSITY OF WASHINGTON · PI CLOWES, ALEXANDER W · 1995 to 2004
$2.2M
Novel Anti-Diabetic Actions of Hypothalamic FGF19-FGFR1 SignalingR01DK101997 · NIDDK · UNIVERSITY OF WASHINGTON · PI SCHWARTZ, MICHAEL W · 2014 to 2018
$1.9M
Hypothalamic Inflammation and Energy HomeostasisR01DK090320 · NIDDK · UNIVERSITY OF WASHINGTON · PI SCHWARTZ, MICHAEL W · 2010 to 2014
$1.8M
VASP: Regulator of Vascular Smooth Muscle Cell FunctionR01HL052459 · NHLBI · UNIVERSITY OF WASHINGTON · PI CLOWES, ALEXANDER W · 1995 to 2008
$1.8M
Acute Renal Failure: An Endotoxin Hyper-Responsive StateR01DK083310 · NIDDK · UNIVERSITY OF WASHINGTON · PI BOMSZTYK, KAROL, ZAGER, RICHARD A. · 2010 to 2013
$1.5M
IKKBeta Mediated Impairment of Endothelial Nitric Oxide ProductionR01DK073878 · NIDDK · UNIVERSITY OF WASHINGTON · PI KIM, FRANCIS · 2006 to 2010
$1.4M
NHLBI NIH HHS HL-52459NHLBI NIH HHS R01 HL052459NHLBI NIH HHS R37 HL052459NHLBI NIH HHS T32 HL007828NHLBI NIH HHS T32-HL-07828NIDDK NIH HHS DK-035816NIDDK NIH HHS DK-068384NIDDK NIH HHS DK-073878NIDDK NIH HHS DK-076169NIDDK NIH HHS DK-083042NIDDK NIH HHS DK-083310NIDDK NIH HHS DK-090320NIDDK NIH HHS DK-101997NIDDK NIH HHS DK-17047NIDDK NIH HHS P01 DK068384NIDDK NIH HHS P30 DK017047NIDDK NIH HHS P30 DK035816NIDDK NIH HHS R01 DK073878NIDDK NIH HHS R01 DK083042NIDDK NIH HHS R01 DK083310NIDDK NIH HHS R01 DK090320NIDDK NIH HHS R01 DK101997NIDDK NIH HHS U24 DK076169
6 · The paper itself

Abstract

Endothelial nitric oxide (NO) signaling plays a physiological role in limiting obesity-associated insulin resistance and inflammation. This study was undertaken to investigate whether this NO effect involves polarization of macrophages toward an anti-inflammatory M2 phenotype. Mice with transgenic endothelial NO synthase overexpression were protected against high-fat diet (HFD)-induced hepatic inflammation and insulin resistance, and this effect was associated with reduced proinflammatory M1 and increased anti-inflammatory M2 activation of Kupffer cells. In cell culture studies, exposure of macrophages to endothelial NO similarly reduced inflammatory (M1) and increased anti-inflammatory (M2) gene expression. Similar effects were induced by macrophage overexpression of vasodilator-stimulated phosphoprotein (VASP), a key downstream mediator of intracellular NO signaling. Conversely, VASP deficiency induced proinflammatory M1 macrophage activation, and the transplantation of bone marrow from VASP-deficient donor mice into normal recipients caused hepatic inflammation and insulin resistance resembling that induced in normal mice by consumption of an HFD. These data suggest that proinflammatory macrophage M1 activation and macrophage-mediated inflammation are tonically inhibited by NO → VASP signal transduction, and that reduced NO → VASP signaling is involved in the effect of HFD feeding to induce M1 activation of Kupffer cells and associated hepatic inflammation. Our data implicate endothelial NO → VASP signaling as a physiological determinant of macrophage polarization and show that signaling via this pathway is required to prevent hepatic inflammation and insulin resistance.

Indexed as

AnimalsCell PolarityEndothelium, VascularInflammationInflammation MediatorsInsulin ResistanceKupffer CellsLiverMacrophage ActivationMacrophagesMiceMice, TransgenicNitric OxideNitric Oxide Synthase Type IIISignal TransductionTriglyceridesInflammation MediatorsNitric OxideNitric Oxide Synthase Type IIITriglycerides

Identifiers

PMID25845662
PMCPMC4512216
OpenAlexW2140299953

What OpenQuestion holds

Textmetadata
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.