Evidence map›Paper›PMID 30295646›Full record

ArticleThe Journal of clinical investigation2018

Endothelial cell α-globin and its molecular chaperone α-hemoglobin-stabilizing protein regulate arteriolar contractility.

Christophe Lechauve, Joshua T Butcher, Abdullah Freiwan, Lauren A Biwer, Julia M Keith, Miranda E Good, Hans Ackerman, Heather S Tillman, Laurent Kiger, Brant E Isakson and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

30 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Article
  3. Endothelial Cell Secretome Alterations Induced by Inflammatory Stress.bioRxiv : the preprint server for biology · 2026
    Article
  4. Elastin Regulation of Vasoreactivity in Resistance Arteries.Hypertension (Dallas, Tex. : 1979) · 2025
    Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Redox-Regulation of α-Globin in Vascular Physiology.Antioxidants (Basel, Switzerland) · 2022
    Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Christophe LechauveDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Joshua T ButcherRobert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Abdullah FreiwanDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Lauren A BiwerRobert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Julia M KeithDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Miranda E GoodRobert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Hans AckermanLaboratory of Malaria and Vector Research, National Institutes of Allergy and Infectious Diseases, Rockville, Maryland, USA.
Heather S TillmanDepartment of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Laurent KigerINSERM, U955 - EFS, Creteil, France.
Brant E IsaksonRobert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Mitchell J WeissDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
St. Jude Children's Research Hospital · USUniversity of Virginia · USInserm · FRNational Institute of Allergy and Infectious Diseases · US

Funding

Nitric Oxide and Endothelial Function in Patients with MalariaZIAAI001150 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI ACKERMAN, HANS · 2011 to 2025
$19.4M
STRUCTURAL STUDIES ON NITRIC OXIDE SYNTHASER01GM057353 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI POULOS, THOMAS L · 1998 to 2018
$6.8M
Trim58 and the Ubiquitin Proteasome System in Erythro-megakaryopoiesisR01DK061692 · NIDDK · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI WEISS, MITCHELL J · 2002 to 2018
$5.6M
Mechanisms of Heterocellular Signaling at the Myoenothelial JunctionR01HL088554 · NHLBI · UNIVERSITY OF VIRGINIA · PI ISAKSON, BRANT E, WEISS, MITCHELL J · 2008 to 2017
$3.8M
NHLBI NIH HHS R01 HL088554NIDDK NIH HHS R01 DK061692NIGMS NIH HHS R01 GM057353
6 · The paper itself

Abstract

Arteriolar endothelial cell-expressed (EC-expressed) α-globin binds endothelial NOS (eNOS) and degrades its enzymatic product, NO, via dioxygenation, thereby lessening the vasodilatory effects of NO on nearby vascular smooth muscle. Although this reaction potentially affects vascular physiology, the mechanisms that regulate α-globin expression and dioxygenase activity in ECs are unknown. Without β-globin, α-globin is unstable and cytotoxic, particularly in its oxidized form, which is generated by dioxygenation and recycled via endogenous reductases. We show that the molecular chaperone α-hemoglobin-stabilizing protein (AHSP) promotes arteriolar α-globin expression in vivo and facilitates its reduction by eNOS. In Ahsp-/- mice, EC α-globin was decreased by 70%. Ahsp-/- and Hba1-/- mice exhibited similar evidence of increased vascular NO signaling, including arteriolar dilation, blunted α1-adrenergic vasoconstriction, and reduced blood pressure. Purified α-globin bound eNOS or AHSP, but not both together. In ECs in culture, eNOS or AHSP enhanced α-globin expression posttranscriptionally. However, only AHSP prevented oxidized α-globin precipitation in solution. Finally, eNOS reduced AHSP-bound α-globin approximately 6-fold faster than did the major erythrocyte hemoglobin reductases (cytochrome B5 reductase plus cytochrome B5). Our data support a model whereby redox-sensitive shuttling of EC α-globin between AHSP and eNOS regulates EC NO degradation and vascular tone.

Indexed as

Models, CardiovascularMuscle ContractionSignal Transductionalpha-GlobinsAnimalsArteriolesEndothelial CellsMiceMice, KnockoutMolecular ChaperonesNitric OxideNitric Oxide Synthase Type IIIAhsp protein, mousealpha-GlobinsMolecular ChaperonesNitric OxideNitric Oxide Synthase Type IIINos3 protein, mouseendothelial cellsHematologyProtein misfoldingVascular Biology

Identifiers

PMID30295646
PMCPMC6205378
OpenAlexW2895728427

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.