Evidence map›Paper›PMID 30470436›Full record

ArticleKidney international2019

α-galactosidase A deficiency promotes von Willebrand factor secretion in models of Fabry disease.

Justin J Kang, Nayiri M Kaissarian, Karl C Desch, Robert J Kelly, Liming Shu, Peter F Bodary, James A Shayman

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Kidney international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

15 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Review
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  4. Article
  5. Review
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  7. Article
  8. Role of UDP-glucose ceramide glucosyltransferase in venous malformation.Frontiers in cell and developmental biology · 2023
    Article
  9. Review
  10. Review
  11. Article
  12. Lysosomal storage diseases: current therapies and future alternatives.Journal of molecular medicine (Berlin, Germany) · 2020
    Review
  13. Article
  14. Progress in the understanding and treatment of Fabry disease.Biochimica et biophysica acta. General subjects · 2020
    Review
  15. 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

7 authors at 1 institution in 1 country.

Justin J KangSchool of Kinesiology, University of Michigan, Ann Arbor, Michigan, USA.
Nayiri M KaissarianDepartment of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA.
Karl C DeschDepartment of Pediatrics and Communicable Disease, University of Michigan, Ann Arbor, Michigan, USA.
Robert J KellyDepartment of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA.
Liming ShuDivision of Nephrology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Peter F BodarySchool of Kinesiology, University of Michigan, Ann Arbor, Michigan, USA.
James A ShaymanDivision of Nephrology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA. Electronic address: jshayman@umich.edu.
University of Michigan–Ann Arbor · US

Funding

THE PHARMACOLOGIC TREATMENT OF FABRY DISEASER01DK055823 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHAYMAN, JAMES ALAN · 2000 to 2013
$4.1M
The Molecular Genetics of Venous Thromboembolic DiseaseR01HL141399 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DESCH, KARL C · 2018 to 2022
$1.9M
NHLBI NIH HHS R01 HL141399NIDDK NIH HHS R01 DK055823
6 · The paper itself

Abstract

Fabry disease results from loss of activity of the lysosomal enzyme α-galactosidase A (GLA), leading to the accumulation of globoseries glycosphingolipids in vascular endothelial cells. Thrombosis and stroke are life-threatening complications of Fabry disease; however, the mechanism of the vasculopathy remains unclear. We explored the relationship between GLA deficiency and endothelial cell von Willebrand factor (VWF) secretion in in vivo and in vitro models of Fabry disease. Plasma VWF was significantly higher at two months and increased with age in Gla-null compared to wild-type mice. Disruption of GLA in a human endothelial cell line by siRNA and CRISPR/Cas9 resulted in a 3-fold and 5-fold increase in VWF secretion, respectively. The increase in VWF levels was associated with decreased endothelial nitric oxide synthase (eNOS) activity in both in vitro models. Pharmacological approaches that increase nitric oxide bioavailability or decrease reactive oxygen species completely normalized the elevated VWF secretion in GLA deficient cells. In contrast, the abnormality was not readily reversed by recombinant human GLA or by inhibition of glycosphingolipid synthesis with eliglustat. These results suggest that GLA deficiency promotes VWF secretion through eNOS dysregulation, which may contribute to the vasculopathy of Fabry disease.

Indexed as

alpha-GalactosidaseAnimalsCell LineDisease Models, AnimalEndothelial CellsEndothelium, VascularFabry DiseaseGlucosyltransferasesGlycosphingolipidsHumansMaleMiceMice, Inbred C57BLMice, KnockoutNitric OxideNitric Oxide Synthase Type IIIalpha-Galactosidaseceramide glucosyltransferaseeliglustatGLA protein, humanGlucosyltransferasesGlycosphingolipidsNitric OxideNitric Oxide Synthase Type IIINOS3 protein, humanPyrrolidinesReactive Oxygen SpeciesRNA, Small Interferingvon Willebrand Factorcerebrovascular diseaseeNOS uncouplinglysosomal storage disordernitric oxidereactive nitrogen speciesreactive oxygen species

Identifiers

PMID30470436
PMCPMC6320285
OpenAlexW2900543309

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.