Evidence map›Paper›PMID 34297830›Full record

ArticleEuropean heart journal2021

Glucosylceramide synthase deficiency in the heart compromises β1-adrenergic receptor trafficking.

Linda Andersson, Mathieu Cinato, Ismena Mardani, Azra Miljanovic, Muhammad Arif, Ara Koh, Malin Lindbom, Marion Laudette, Entela Bollano, Elmir Omerovic and 19 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European heart journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 15% 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

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. The role of sphingolipids in heart failure.European heart journal open · 2025
    Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Regulation of cellular and systemic sphingolipid homeostasis.Nature reviews. Molecular cell biology · 2024
    Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Role of UDP-glucose ceramide glucosyltransferase in venous malformation.Frontiers in cell and developmental biology · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors at 9 institutions in 5 countries.

Linda AnderssonDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.
Mathieu CinatoDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.ORCID 0000-0002-8490-4335
Ismena MardaniDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.
Azra MiljanovicDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.
Muhammad ArifScience for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden.ORCID 0000-0003-2261-0881
Ara KohDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.ORCID 0000-0001-7673-034X
Malin LindbomDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.
Marion LaudetteDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.
Entela BollanoDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.ORCID 0000-0003-3341-2434
Elmir OmerovicDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.ORCID 0000-0002-3875-8621
Martina KlevstigDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.
Marcus HenricssonDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.ORCID 0000-0002-4202-0339
Per FogelstrandDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.
Karl SwärdDepartment of Experimental Medical Science, Lund University, SE-221 84 Lund, Sweden.
Matias EkstrandDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.ORCID 0000-0002-0403-9266
Max LevinDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.ORCID 0000-0001-9676-5582
Johannes WikströmBioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
Stephen DoranCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London SE1 9RT, UK.ORCID 0000-0002-9236-5407
Tuulia HyötyläinenSchool of Natural Sciences and Technology, Örebro University, Fakultetsgatan 1, SE-701 82 Örebro, Sweden.ORCID 0000-0002-1389-8302
Lisanna SinisaluSchool of Natural Sciences and Technology, Örebro University, Fakultetsgatan 1, SE-701 82 Örebro, Sweden.
Matej OrešičSchool of Medical Sciences, Örebro University, SE-701 82 Örebro, Sweden.ORCID 0000-0002-2856-9165
Åsa TivestenDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.ORCID 0000-0002-8318-0486
Martin AdielsDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.ORCID 0000-0002-3667-589X
Martin O BergoDepartment of Biosciences and Nutrition, Karolinska Institute, SE-141 83 Huddinge, Sweden.ORCID 0000-0002-6915-7140
Richard ProiaNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0003-0456-1270
Adil MardinogluScience for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden.
Anders JeppssonDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.ORCID 0000-0003-2356-2295
Jan BorénDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.
Malin C LevinDepartment of Molecular and Clinical Medicine/Wallenberg Laboratory, Institute of Medicine, the Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital, Bruna Stråket 16, SE-413 45 Gothenburg, Sweden.
Sahlgrenska University Hospital · SEKing's College London · GBÖrebro University · SEAstraZeneca (Sweden) · SEKarolinska Institutet · SELund University · SENational Institutes of Health · USScience for Life Laboratory · SEUniversity of Turku · FI

Funding

Mouse Models of Novel Sphingolipid Biology and Disease MechanismsZIADK056014 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI PROIA, RICHARD · 2009 to 2025
$10.6M
6 · The paper itself

Abstract

aimsCardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function. METHODS AND

resultsUsing human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors.

conclusionsOur findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.

Indexed as

GlucosyltransferasesMyocytes, CardiacAnimalsCardiomegalyMiceReceptors, Adrenergicceramide glucosyltransferaseGlucosyltransferasesReceptors, AdrenergicAdrenergicAutophagyBetaCardiac dysfunctionEndolysosomal traffickingGlycosphingolipidsLipidsReceptors

Identifiers

PMID34297830
PMCPMC8599074
OpenAlexW3186088302

What OpenQuestion holds

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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.