Evidence map›Paper›PMID 33980990›Full record

ArticlePediatric research2022

Angiopoietin-1 protects against endotoxin-induced neonatal lung injury and alveolar simplification in mice.

Umar Salimi, Heather L Menden, Sherry M Mabry, Sheng Xia, Venkatesh Sampath

Abstract read
In one paragraph

Article in Pediatric research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

11 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Role of Tie-2 Axis in Sepsis: A Potential Therapeutic Target.Journal of cellular and molecular medicine · 2025
    Review
  4. Article
  5. A Multimodal Spatial and Epigenomic Atlas of Human Adult Lung Topography.bioRxiv : the preprint server for biology · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Silencing ANGPT2 alleviates ulcerative colitis by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024
    Article
  10. Article
  11. Review
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

5 authors.

Umar Salimi *Division of Pediatric Critical Care, Department of Pediatrics, Children's Mercy Kansas City, Kansas, MO, USA.
Heather L Menden *Division of Neonatology, Department of Pediatrics, Children's Mercy Kansas City, Kansas, MO, USA.
Sherry M MabryDivision of Neonatology, Department of Pediatrics, Children's Mercy Kansas City, Kansas, MO, USA.
Sheng XiaDivision of Neonatology, Department of Pediatrics, Children's Mercy Kansas City, Kansas, MO, USA.
Venkatesh SampathDivision of Neonatology, Department of Pediatrics, Children's Mercy Kansas City, Kansas, MO, USA. vsampath@cmh.edu.

Funding

Inflammatory Angiogenesis in the LungR01HL128374 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI SAMPATH, VENKATESH · 2015 to 2020
$1.8M
NHLBI NIH HHS R01 HL128374
6 · The paper itself

Abstract

backgroundSepsis in premature newborns is a risk factor for bronchopulmonary dysplasia (BPD), but underlying mechanisms of lung injury remain unclear. Aberrant expression of endothelial cell (EC) angiopoietin 2 (ANGPT2) disrupts angiopoietin 1 (ANGPT1)/TIE2-mediated endothelial quiescence, and is implicated in sepsis-induced acute respiratory distress syndrome in adults. We hypothesized that recombinant ANGPT1 will mitigate sepsis-induced ANGPT2 expression, inflammation, acute lung injury (ALI), and alveolar remodeling in the saccular lung.

methodsEffects of recombinant ANGPT1 on lipopolysaccharide (LPS)-induced endothelial inflammation were evaluated in human pulmonary microvascular endothelial cells (HPMEC). ALI and long-term alveolar remodeling were assessed in newborn mice exposed to intraperitoneal LPS and recombinant ANGPT1 pretreatment.

resultsLPS dephosphorylated EC TIE2 in association with increased ANGPT2 in vivo and in vitro. ANGPT1 suppressed LPS and ANGPT2-induced EC inflammation in HPMEC. Neonatal mice treated with LPS had increased lung cytokine expression, neutrophilic influx, and cellular apoptosis. ANGPT1 pre-treatment suppressed LPS-induced lung Toll-like receptor signaling, inflammation, and ALI. LPS-induced acute increases in metalloproteinase 9 expression and elastic fiber breaks, as well as a long-term decrease in radial alveolar counts, were mitigated by ANGPT1.

conclusionsIn an experimental model of sepsis-induced BPD, ANGPT1 preserved endothelial quiescence, inhibited ALI, and suppressed alveolar simplification. IMPACT: Key message: Angiopoietin 1 inhibits LPS-induced neonatal lung injury and alveolar remodeling. Additions to existing literature: Demonstrates dysregulation of angiopoietin-TIE2 axis is important for sepsis- induced acute lung injury and alveolar simplification in experimental BPD. Establishes recombinant Angiopoietin 1 as an anti-inflammatory therapy in BPD. IMPACT: Angiopoietin 1-based interventions may represent novel therapies for mitigating sepsis-induced lung injury and BPD in premature infants.

Indexed as

Acute Lung InjuryBronchopulmonary DysplasiaSepsisAngiopoietin-1Angiopoietin-2AnimalsEndothelial CellsEndotoxinsHumansInfant, NewbornInflammationLipopolysaccharidesLungMiceAngiopoietin-1Angiopoietin-2EndotoxinsLipopolysaccharides

Identifiers

PMID33980990
PMCPMC8586034

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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.