Evidence map›Paper›PMID 26930027›Full record

ArticleJournal of molecular and cellular cardiology2016

Targeting acid sphingomyelinase reduces cardiac ceramide accumulation in the post-ischemic heart.

Martina Klevstig, Marcus Ståhlman, Annika Lundqvist, Margareta Scharin Täng, Per Fogelstrand, Martin Adiels, Linda Andersson, Richard Kolesnick, Anders Jeppsson, Jan Borén and 1 more

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

Article in Journal of molecular and cellular cardiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

28 citing papers in PubMed, 56 citations in OpenAlex.

  1. Article
  2. Review
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  6. Article
  7. Article
  8. Article
  9. Review
  10. Modified mRNA Therapeutics for Heart Diseases.International journal of molecular sciences · 2022
    Review
  11. Potential Drug Targets for Ceramide Metabolism in Cardiovascular Disease.Journal of cardiovascular development and disease · 2022
    Review
  12. Article
  13. Article
  14. Article
  15. Metabolomic profiling of patients with high gradient aortic stenosis undergoing transcatheter aortic valve replacement.Clinical research in cardiology : official journal of the German Cardiac Society · 2021
    Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article
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

11 authors at 2 institutions in 2 countries.

Martina KlevstigDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, 413 45 Gothenburg, Sweden.
Marcus StåhlmanDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, 413 45 Gothenburg, Sweden.
Annika LundqvistDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, 413 45 Gothenburg, Sweden.
Margareta Scharin TängDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, 413 45 Gothenburg, Sweden.
Per FogelstrandDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, 413 45 Gothenburg, Sweden.
Martin AdielsDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, 413 45 Gothenburg, Sweden.
Linda AnderssonDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, 413 45 Gothenburg, Sweden.
Richard KolesnickMemorial Sloan Kettering Cancer Center, NY, USA.
Anders JeppssonDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, 413 45 Gothenburg, Sweden; Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden.
Jan BorénDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, 413 45 Gothenburg, Sweden.
Malin C LevinDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, 413 45 Gothenburg, Sweden. Electronic address: malin.levin@wlab.gu.se.
University of Gothenburg · SEMemorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Intramural NIH HHS NIH0010513932NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Ceramide accumulation is known to accompany acute myocardial ischemia, but its role in the pathogenesis of ischemic heart disease is unclear. In this study, we aimed to determine how ceramides accumulate in the ischemic heart and to determine if cardiac function following ischemia can be improved by reducing ceramide accumulation. To investigate the association between ceramide accumulation and heart function, we analyzed myocardial left ventricle biopsies from subjects with chronic ischemia and found that ceramide levels were higher in biopsies from subjects with reduced heart function. Ceramides are produced by either de novo synthesis or hydrolysis of sphingomyelin catalyzed by acid and/or neutral sphingomyelinase. We used cultured HL-1 cardiomyocytes to investigate these pathways and showed that acid sphingomyelinase activity rather than neutral sphingomyelinase activity or de novo sphingolipid synthesis was important for hypoxia-induced ceramide accumulation. We also used mice with a partial deficiency in acid sphingomyelinase (Smpd1(+/-) mice) to investigate if limiting ceramide accumulation under ischemic conditions would have a beneficial effect on heart function and survival. Although we showed that cardiac ceramide accumulation was reduced in Smpd1(+/-) mice 24h after an induced myocardial infarction, this reduction was not accompanied by an improvement in heart function or survival. Our findings show that accumulation of cardiac ceramides in the post-ischemic heart is mediated by acid sphingomyelinase. However, targeting ceramide accumulation in the ischemic heart may not be a beneficial treatment strategy.

Indexed as

AnimalsCeramidesGenotypeHypoxiaMiceMice, KnockoutMortalityMutationMyocardial IschemiaMyocardiumSphingomyelin PhosphodiesteraseVentricular DysfunctionCeramidesSphingomyelin PhosphodiesteraseAcid sphingomyelinaseBioactive lipidsCeramideMyocardial ischemia

Identifiers

PMID26930027
PMCPMC5026316
OpenAlexW2275702678

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.