Evidence map›Paper›PMID 20431061›Full record

ArticleCirculation research2010

Endothelial nitric oxide synthase deficiency causes collateral vessel rarefaction and impairs activation of a cell cycle gene network during arteriogenesis.

Xuming Dai, James E Faber

Abstract read
In one paragraph

Article in Circulation research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 1 pooled it
11.2field-weighted citation impact, top 1% 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

83 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.

  1. Pooled it
  2. Genetic determinants of insufficiency of the collateral circulation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026
    Review
  3. Review
  4. Article
  5. Sanctuary sites in cortical stroke.Frontiers in neurology · 2025
    Article
  6. The Implications of Aging on Vascular Health.International journal of molecular sciences · 2024
    Review
  7. Article
  8. Article
  9. Increasing nitric oxide bioavailability fails to improve collateral vessel formation in humanized sickle cell mice.Laboratory investigation; a journal of technical methods and pathology · 2022
    Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. The Roles of AMPK in Revascularization.Cardiology research and practice · 2020
    Review

23 more citing papers are in PubMed but not listed here.

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

2 authors at 1 institution in 1 country.

Xuming DaiDepartment of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, 111 Mason Farm Rd, CB #7545, Chapel Hill, NC 27599, USA. xmdai3@med.unc.edu
James E Faber
University of North Carolina at Chapel Hill · US

Funding

ALPHA ADRENOCEPTORS IN VASCULAR WALL GROWTHR01HL062584 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FABER, JAMES E · 1999 to 2011
$4.6M
Mechanisms of Collateral Development and Collateral Growth in IschemiaR01HL090655 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FABER, JAMES E · 2008 to 2011
$2.0M
UNC-Clinician-Scientist Training Program in Cardiovascular MedicineT32HL083828 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI STOUFFER, GEORGE A · 2006 to 2015
$2.0M
NHLBI NIH HHS HL090655NHLBI NIH HHS HL62584NHLBI NIH HHS NIH T32 HL083828-04NHLBI NIH HHS R01 HL062584NHLBI NIH HHS R01 HL090655NHLBI NIH HHS T32 HL083828
6 · The paper itself

Abstract

rationaleThe collateral circulation is tissue- and life-saving in obstructive arterial disease. Disappointing outcomes in clinical trials aimed at augmenting collateral growth highlight the need for greater understanding of collateral biology.

objectiveThe role of endothelial nitric oxide synthase (eNOS) in forming native (preexisting) collaterals and remodeling in obstructive disease are unknown or controversial issues, respectively. METHODS AND

resultsWe compared the native collateral circulation in healthy tissue and collateral remodeling after femoral artery ligation (FAL) in wild-type and eNOS-knockout (KO) mice. Perfusion after FAL fell further in adult eNOS-KOs, in association with fewer native collaterals in hindlimb (confirmed in brain). This was not attributable to impaired collateral formation in the embryo-neonate, but rather from collateral loss during growth to adulthood. Compared to wild-type, eNOS-KOs evidenced reduced collateral remodeling, angiogenesis, and flow-mediated dilation of the arterial bed supplying the collaterals, resulting in lower perfusion and greater ischemic injury at all time points over 21 days following FAL. To probe the mechanism for impaired remodeling, we performed genome-wide expression profiling of isolated, remodeling hindlimb collaterals 24 hour after FAL. Upregulation of genes encoding cytokines/chemokines, inflammatory, stress response, and cell cycle proteins was evident in wild-type mice. In contrast, expression was lower in 40 of 44 cell cycle genes in eNOS-KO mice, in association with impaired proliferation of vascular wall cells.

conclusionsOur findings suggest a novel role for eNOS in maintaining native collateral density during natural growth to adulthood and in collateral remodeling in obstructive disease, the latter through regulation of cell proliferation.

Indexed as

AngiographyAnimalsArteriesCell CycleCell ProliferationCollateral CirculationFemoral ArteryGene Expression ProfilingGenes, cdcHindlimbIschemiaLigationMiceMice, Inbred C57BLMice, KnockoutModels, AnimalNitric Oxide Synthase Type III

Identifiers

PMID20431061
PMCPMC3401938
OpenAlexW2133979273

What OpenQuestion holds

Textmetadata
LicenceTDM
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.