Evidence map›Paper›PMID 26338297›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2015

Mechanisms of Amplified Arteriogenesis in Collateral Artery Segments Exposed to Reversed Flow Direction.

Joshua L Heuslein, Joshua K Meisner, Xuanyue Li, Ji Song, Helena Vincentelli, Ryan J Leiphart, Elizabeth G Ames, Brett R Blackman, Brett R Blackman, Richard J Price

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–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

16 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Vascular Regeneration in Peripheral Artery Disease.Arteriosclerosis, thrombosis, and vascular biology · 2020
    Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. MicroRNA-146a Regulates Perfusion Recovery in Response to Arterial OcclusionFrontiers in bioengineering and biotechnology · 2018
    Article
  14. Article
  15. Article
  16. Article
4 · The record

Corrections and comments

  • Erratum issued
    Correction.2015 · Blackman, Brett R [added]
5 · Who and what money

Authors and funding

10 authors.

Joshua L HeusleinFrom the Departments of Biomedical Engineering (J.L.H., J.K.M., X.L., J.S., H.V., R.J.L., E.G.A., R.J.P.), Molecular Physiology and Biological Physics (E.G.A.), Radiology (R.J.P.), and Radiation Oncology (R.J.P.), University of Virginia, Charlottesville; and HemoShear Therapeutics LLC, Charlottesville, VA (B.R.B.).
Joshua K MeisnerFrom the Departments of Biomedical Engineering (J.L.H., J.K.M., X.L., J.S., H.V., R.J.L., E.G.A., R.J.P.), Molecular Physiology and Biological Physics (E.G.A.), Radiology (R.J.P.), and Radiation Oncology (R.J.P.), University of Virginia, Charlottesville; and HemoShear Therapeutics LLC, Charlottesville, VA (B.R.B.).
Xuanyue LiFrom the Departments of Biomedical Engineering (J.L.H., J.K.M., X.L., J.S., H.V., R.J.L., E.G.A., R.J.P.), Molecular Physiology and Biological Physics (E.G.A.), Radiology (R.J.P.), and Radiation Oncology (R.J.P.), University of Virginia, Charlottesville; and HemoShear Therapeutics LLC, Charlottesville, VA (B.R.B.).
Ji SongFrom the Departments of Biomedical Engineering (J.L.H., J.K.M., X.L., J.S., H.V., R.J.L., E.G.A., R.J.P.), Molecular Physiology and Biological Physics (E.G.A.), Radiology (R.J.P.), and Radiation Oncology (R.J.P.), University of Virginia, Charlottesville; and HemoShear Therapeutics LLC, Charlottesville, VA (B.R.B.).
Helena VincentelliFrom the Departments of Biomedical Engineering (J.L.H., J.K.M., X.L., J.S., H.V., R.J.L., E.G.A., R.J.P.), Molecular Physiology and Biological Physics (E.G.A.), Radiology (R.J.P.), and Radiation Oncology (R.J.P.), University of Virginia, Charlottesville; and HemoShear Therapeutics LLC, Charlottesville, VA (B.R.B.).
Ryan J LeiphartFrom the Departments of Biomedical Engineering (J.L.H., J.K.M., X.L., J.S., H.V., R.J.L., E.G.A., R.J.P.), Molecular Physiology and Biological Physics (E.G.A.), Radiology (R.J.P.), and Radiation Oncology (R.J.P.), University of Virginia, Charlottesville; and HemoShear Therapeutics LLC, Charlottesville, VA (B.R.B.).
Elizabeth G AmesFrom the Departments of Biomedical Engineering (J.L.H., J.K.M., X.L., J.S., H.V., R.J.L., E.G.A., R.J.P.), Molecular Physiology and Biological Physics (E.G.A.), Radiology (R.J.P.), and Radiation Oncology (R.J.P.), University of Virginia, Charlottesville; and HemoShear Therapeutics LLC, Charlottesville, VA (B.R.B.).
Brett R BlackmanFrom the Departments of Biomedical Engineering (J.L.H., J.K.M., X.L., J.S., H.V., R.J.L., E.G.A., R.J.P.), Molecular Physiology and Biological Physics (E.G.A.), Radiology (R.J.P.), and Radiation Oncology (R.J.P.), University of Virginia, Charlottesville; and HemoShear Therapeutics LLC, Charlottesville, VA (B.R.B.).
Brett R Blackman
Richard J PriceFrom the Departments of Biomedical Engineering (J.L.H., J.K.M., X.L., J.S., H.V., R.J.L., E.G.A., R.J.P.), Molecular Physiology and Biological Physics (E.G.A.), Radiology (R.J.P.), and Radiation Oncology (R.J.P.), University of Virginia, Charlottesville; and HemoShear Therapeutics LLC, Charlottesville, VA (B.R.B.). rprice@virginia.edu.

Funding

BASIC CARDIOVASCULAR RESEARCH TRAINING GRANTT32HL007284 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Brant E Isakson, Gary K Owens · 1985 to 2026
$19.6M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007267 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GARCIA-BLANCO, MARIANO A. · 1985 to 2024
$13.4M
Molecular Transducers Linking Shear Stress to Capillary Sprouting and StabilityR21HL098632 · NHLBI · UNIVERSITY OF VIRGINIA · PI PRICE, RICHARD J. · 2010 to 2011
$424k
Application of Laser Speckle Flowmetry to Vascular RemodelingR03EB017927 · NIBIB · UNIVERSITY OF VIRGINIA · PI PRICE, RICHARD J. · 2014 to 2015
$153k
NHLBI NIH HHS R21 HL098632NHLBI NIH HHS R21-HL098632NHLBI NIH HHS T32 HL007284NHLBI NIH HHS T32-HL007284NIBIB NIH HHS R03 EB017927NIBIB NIH HHS R03-EB017927NIGMS NIH HHS T32 GM007267NIGMS NIH HHS T32-GM007267
6 · The paper itself

Abstract

objectiveCollateral arteriogenesis, the growth of existing arterial vessels to a larger diameter, is a fundamental adaptive response that is often critical for the perfusion and survival of tissues downstream of chronic arterial occlusion(s). Shear stress regulates arteriogenesis; however, the arteriogenic significance of reversed flow direction, occurring in numerous collateral artery segments after femoral artery ligation, is unknown. Our objective was to determine if reversed flow direction in collateral artery segments differentially regulates endothelial cell signaling and arteriogenesis. APPROACH AND

resultsCollateral segments experiencing reversed flow direction after femoral artery ligation in C57BL/6 mice exhibit increased pericollateral macrophage recruitment, amplified arteriogenesis (30% diameter and 2.8-fold conductance increases), and remarkably permanent (12 weeks post femoral artery ligation) remodeling. Genome-wide transcriptional analyses on human umbilical vein endothelial cells exposed to reversed flow conditions mimicking those occurring in vivo yielded 10-fold more significantly regulated transcripts, as well as enhanced activation of upstream regulators (nuclear factor κB [NFκB], vascular endothelial growth factor, fibroblast growth factor-2, and transforming growth factor-β) and arteriogenic canonical pathways (protein kinase A, phosphodiesterase, and mitogen-activated protein kinase). Augmented expression of key proarteriogenic molecules (Kruppel-like factor 2 [KLF2], intercellular adhesion molecule 1, and endothelial nitric oxide synthase) was also verified by quantitative real-time polymerase chain reaction, leading us to test whether intercellular adhesion molecule 1 or endothelial nitric oxide synthase regulate amplified arteriogenesis in flow-reversed collateral segments in vivo. Interestingly, enhanced pericollateral macrophage recruitment and amplified arteriogenesis was attenuated in flow-reversed collateral segments after femoral artery ligation in intercellular adhesion molecule 1(-/-) mice; however, endothelial nitric oxide synthase(-/-) mice showed no such differences.

conclusionsReversed flow leads to a broad amplification of proarteriogenic endothelial signaling and a sustained intercellular adhesion molecule 1-dependent augmentation of arteriogenesis. Further investigation of the endothelial mechanotransduction pathways activated by reversed flow may lead to more effective and durable therapeutic options for arterial occlusive diseases.

Indexed as

Collateral CirculationMechanotransduction, CellularNeovascularization, PhysiologicAnimalsArteriesBlood Flow VelocityCells, CulturedDisease Models, AnimalFemoral ArteryGene Expression RegulationHindlimbHumansHuman Umbilical Vein Endothelial CellsIntercellular Adhesion Molecule-1IschemiaLigationICAM1 protein, humanIcam1 protein, mouseIntercellular Adhesion Molecule-1NF-kappa BNitric Oxide Synthase Type IIINOS3 protein, humanNos3 protein, mouseendothelial cellsfemoral arterygene expressionhemodynamicsperipheral arterial disease

Identifiers

PMID26338297
PMCPMC4618717

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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.