Evidence map›Paper›PMID 24004504›Full record

ArticleCirculation2013

Homoarginine levels are regulated by L-arginine:glycine amidinotransferase and affect stroke outcome: results from human and murine studies.

Chi-un Choe, Dorothee Atzler, Philipp S Wild, Angela M Carter, Rainer H Böger, Francisco Ojeda, Olga Simova, Malte Stockebrand, Karl Lackner, Christine Nabuurs and 15 more

Open access · greenAbstract readComparative StudyMulticenter Study
PubMed Publisher
In one paragraph

Article in Circulation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 2 pooled it
7.4field-weighted citation impact, top 2% 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

58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 141 citations in OpenAlex.

  1. Pooled it
  2. Association of Plasma Small-Molecule Intermediate Metabolites With Age and Body Mass Index Across Six Diverse Study Populations.The journals of gerontology. Series A, Biological sciences and medical sciences · 2016
    Pooled it
  3. Oral supplementation with L-homoarginine in young volunteers.British journal of clinical pharmacology · 2016
    Trial
  4. Article
  5. A plasma metabolomic fingerprint of moderate or severe hearing loss.Metabolomics : Official journal of the Metabolomic Society · 2026
    Article
  6. Article
  7. Review
  8. Article
  9. Mechanisms of Homoarginine: Looking Beyond Clinical Outcomes.Acta physiologica (Oxford, England) · 2025
    Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Amino Acids in Health and Disease: The Good, the Bad, and the Ugly.International journal of molecular sciences · 2023
    Article
  19. Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 6 institutions in 3 countries.

Chi-un ChoeDepartments of Neurology (C.C., O.S., C.G., T.M.), Experimental Neuropediatrics (C.C., M.S., D.I.), Department of Clinical Pharmacology and Toxicology (D.A., R.H.B., N.L., R.A.B., E.S.), and German Center for Cardiovascular Research (D.A., P.S.W., R.H.B., S.B., T.Z., E.S.), Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany (F.O., C.M., S. Baldus, S. Blankenberg, T.Z.); Department of Clinical Chemistry, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (T.S.); Department of Cardiology and Angiology (P.S.W.), Gutenberg Health Study (P.S.W.), and Department of Clinical Chemistry (K.L.), Johannes Gutenberg University, Mainz, Germany; Experimental Neurophysiology, University Hospital Cologne, Köln, Germany (D.I.); German Center for Neurodegenerative Diseases, Bonn, Germany (D.I.); Department of Clinical Pharmacy and Pharmacotherapy, Martin-Luther-University Halle Wittenberg, Halle Germany (R.A.B.); Division of Cardiovascular and Diabetes Research, Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, UK (A.M.C., P.J.G.); Department of Radiology, Radboud University Medical Centre Nijmegen, Nijmegen, Netherlands (C.N., A.H.); and Laboratory of Neurochemistry and Behavior, Born-Bunge Foundation, University of Antwerp, Antwerp, Belgium (B.M., P.P. De D.).
Dorothee Atzler
Philipp S Wild
Angela M Carter
Rainer H Böger
Francisco Ojeda
Olga Simova
Malte Stockebrand
Karl Lackner
Christine Nabuurs
Bart Marescau
Thomas Streichert
Christian Müller
Nicole Lüneburg
Peter P De Deyn
Ralf A Benndorf
Stephan Baldus
Christian Gerloff
Stefan Blankenberg
Arend Heerschap
Peter J Grant
Tim Magnus
Tanja Zeller
Dirk Isbrandt
Edzard Schwedhelm
Radboud University Nijmegen · NLMartin Luther University Halle-Wittenberg · DEGerman Center for Neurodegenerative Diseases · DEUniversity Medical Center of the Johannes Gutenberg University Mainz · DEJohannes Gutenberg University Mainz · DEUniversity of Leeds · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEndogenous arginine homologues, including homoarginine, have been identified as novel biomarkers for cardiovascular disease and outcomes. Our studies of human cohorts and a confirmatory murine model associated the arginine homologue homoarginine and its metabolism with stroke pathology and outcome. METHODS AND

resultsIncreasing homoarginine levels were independently associated with a reduction in all-cause mortality in patients with ischemic stroke (7.4 years of follow-up; hazard ratio for 1-SD homoarginine, 0.79 [95% confidence interval, 0.64-0.96]; P=0.019; n=389). Homoarginine was also independently associated with the National Institutes of Health Stroke Scale+age score and 30-day mortality after ischemic stroke (P<0.05; n=137). A genome-wide association study revealed that plasma homoarginine was strongly associated with single nucleotide polymorphisms in the L-arginine:glycine amidinotransferase (AGAT) gene (P<2.1 × 10(-8); n=2806), and increased AGAT expression in a cell model was associated with increased homoarginine. Next, we used 2 genetic murine models to investigate the link between plasma homoarginine and outcome after experimental ischemic stroke: (1) an AGAT deletion (AGAT(-/-)) and (2) a guanidinoacetate N-methyltransferase deletion (GAMT(-/-)) causing AGAT upregulation. As suggested by the genome-wide association study, homoarginine was absent in AGAT(-/-) mice and increased in GAMT(-/-) mice. Cerebral damage and neurological deficits in experimental stroke were increased in AGAT(-/-) mice and attenuated by homoarginine supplementation, whereas infarct size in GAMT(-/-) mice was decreased compared with controls.

conclusionsLow homoarginine appears to be related to poor outcome after ischemic stroke. Further validation in future trials may lead to therapeutic adjustments of homoarginine metabolism that alleviate stroke and other vascular disorders.

Indexed as

AdultAgedAmidinotransferasesAnimalsArginineCohort StudiesDisease Models, AnimalFemaleGenome-Wide Association StudyHEK293 CellsHomoarginineHumansMaleMiceMice, Inbred C57BLMiddle AgedAmidinotransferasesArginineglycine amidinotransferaseHomoargininegenome-wide association studieshomoarginineL-arginine:glycine amidinotransferasesingle nucleotide polymorphismstroke

Identifiers

PMID24004504
OpenAlexW1967651820

What OpenQuestion holds

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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.