Evidence map›Paper›PMID 26817610›Full record

ArticleJournal of vascular surgery2017

Eph-B4 mediates vein graft adaptation by regulation of endothelial nitric oxide synthase.

Mo Wang, Michael J Collins, Trenton R Foster, Hualong Bai, Takuya Hashimoto, Jeans M Santana, Chang Shu, Alan Dardik

Abstract read
In one paragraph

Article in Journal of vascular surgery, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Review
  3. The Pyrazolo[3,4-Molecules (Basel, Switzerland) · 2020
    Article
  4. Review
  5. Arterial Venous Differentiation for Vascular Bioengineering.Annual review of biomedical engineering · 2018
    Review
  6. Article
  7. Review
  8. Membrane-mediated regulation of vascular identity.Birth defects research. Part C, Embryo today : reviews · 2016
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Mo WangDepartment of Vascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, China; Vascular Biology and Therapeutics Program and Department of Surgery, Yale University School of Medicine, New Haven, Conn.
Michael J CollinsVascular Biology and Therapeutics Program and Department of Surgery, Yale University School of Medicine, New Haven, Conn.
Trenton R FosterVascular Biology and Therapeutics Program and Department of Surgery, Yale University School of Medicine, New Haven, Conn.
Hualong BaiVascular Biology and Therapeutics Program and Department of Surgery, Yale University School of Medicine, New Haven, Conn.
Takuya HashimotoVascular Biology and Therapeutics Program and Department of Surgery, Yale University School of Medicine, New Haven, Conn.
Jeans M SantanaVascular Biology and Therapeutics Program and Department of Surgery, Yale University School of Medicine, New Haven, Conn.
Chang ShuDepartment of Vascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
Alan DardikVascular Biology and Therapeutics Program and Department of Surgery, Yale University School of Medicine, New Haven, Conn; Department of Surgery, VA Connecticut Healthcare System, West Haven, Conn. Electronic address: alan.dardik@yale.edu.

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Molecular Regulation of Vein Graft AdapationR01HL095498 · NHLBI · YALE UNIVERSITY · PI DARDIK, ALAN · 2009 to 2013
$2.4M
Molecular regulation of vein graft adaptationR56HL095498 · NHLBI · YALE UNIVERSITY · PI DARDIK, ALAN · 2014 to 2014
$416k
Molecular regulation of fistula adaptation for dialysis accessI01BX002336 · VA · VA CONNECTICUT HEALTHCARE SYSTEM · PI DARDIK, ALAN · 2014 to 2017
–
BLRD VA I01 BX002336NCATS NIH HHS UL1 TR001863NHLBI NIH HHS R01 HL095498NHLBI NIH HHS R56 HL095498
6 · The paper itself

Abstract

objectiveVein graft adaptation is characterized by loss of expression of the tyrosine kinase receptor Eph-B4, the embryonic determinant of venous identity, without increased expression of its ligand ephrin-B2, the embryonic determinant of arterial identity. Endothelial nitric oxide synthase (eNOS) is an important mediator of vessel remodeling. We hypothesized that the mechanism of action of Eph-B4 during vein graft adaptation might be through regulation of downstream eNOS activity.

methodsMouse lung endothelial cells were stimulated with ephrin-B2/Fc, without and with preclustering, without and with the eNOS inhibitor N

resultsEphrin-B2/Fc stimulated both Eph-B4 and eNOS phosphorylation in a bimodal temporal distribution (n = 4; P < .05), with preclustered ephrin-B2/Fc causing prolonged peak Eph-B4 and eNOS phosphorylation as well as altered subcellular localization (n = 4; P < .05). Ephrin-B2/Fc increased NO release (n = 3; P < .01) as well as increased endothelial cell migration (n = 6; P < .05) in an eNOS-dependent fashion. Both human and mouse vein grafts showed increased eNOS phosphorylation compared with normal veins (n = 3; P < .05). Vein grafts from eNOS knockout mice showed less dilation and less wall thickening compared with wild-type vein grafts (n = 7; P < .05).

conclusionseNOS is a mediator of vein graft adaptation to the arterial environment. Eph-B4 stimulates eNOS phosphorylation in vitro and may mediate vein graft adaptation by regulation of eNOS activity in vivo.

Indexed as

Vascular RemodelingAdaptation, PhysiologicalAnimalsCell MovementCells, CulturedEnzyme InhibitorsEphrin-B2GenotypeHumansMice, Inbred C57BLMice, KnockoutNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide Synthase Type IIIPhenotypePhosphorylationEnzyme InhibitorsEphb4 protein, mouseEphrin-B2NG-Nitroarginine Methyl EsterNitric OxideNitric Oxide Synthase Type IIINOS3 protein, humanNos3 protein, mouseReceptor, EphB4

Identifiers

PMID26817610
PMCPMC4958608

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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.