Evidence map›Paper›PMID 23840832›Full record

ArticlePloS one2013

Palmitic acid induces osteoblastic differentiation in vascular smooth muscle cells through ACSL3 and NF-κB, novel targets of eicosapentaenoic acid.

Aiko Kageyama, Hiroki Matsui, Masahiko Ohta, Keisuke Sambuichi, Hiroyuki Kawano, Tatsuto Notsu, Kazunori Imada, Tomoyuki Yokoyama, Masahiko Kurabayashi

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
2.5field-weighted citation impact, top 10% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Role of Stearoyl-CoA Desaturase 1 in Cardiovascular Physiology.International journal of molecular sciences · 2023
    Review
  9. Article
  10. New insight into dyslipidemia-induced cellular senescence in atherosclerosis.Biological reviews of the Cambridge Philosophical Society · 2022
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Observational
  19. Effects of Eicosapentaenoic Acid on Arterial Calcification.International journal of molecular sciences · 2020
    Review
  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

9 authors at 2 institutions in 1 country.

Aiko KageyamaDevelopment Research, Mochida Pharmaceutical Co, Ltd, Gotemba, Shizuoka, Japan.
Hiroki Matsui
Masahiko Ohta
Keisuke Sambuichi
Hiroyuki Kawano
Tatsuto Notsu
Kazunori Imada
Tomoyuki Yokoyama
Masahiko Kurabayashi
Mochida Pharmaceutical (Japan) · JPGunma University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Free fatty acids (FFAs), elevated in metabolic syndrome and diabetes, play a crucial role in the development of atherosclerotic cardiovascular disease, and eicosapentaenoic acid (EPA) counteracts many aspects of FFA-induced vascular pathology. Although vascular calcification is invariably associated with atherosclerosis, the mechanisms involved are not completely elucidated. In this study, we tested the hypothesis that EPA prevents the osteoblastic differentiation and mineralization of vascular smooth muscle cells (VSMC) induced by palmitic acid (PA), the most abundant long-chain saturated fatty acid in plasma. PA increased and EPA abolished the expression of the genes for bone-related proteins, including bone morphogenetic protein (BMP)-2, Msx2 and osteopontin in human aortic smooth muscle cells (HASMC). Among the long-chain acyl-CoA synthetase (ACSL) subfamily, ACSL3 expression was predominant in HASMC, and PA robustly increased and EPA efficiently inhibited ACSL3 expression. Importantly, PA-induced osteoblastic differentiation was mediated, at least in part, by ACSL3 activation because acyl-CoA synthetase (ACS) inhibitor or siRNA targeted to ACSL3 completely prevented the PA induction of both BMP-2 and Msx2. Conversely, adenovirus-mediated ACSL3 overexpression enhanced PA-induced BMP-2 and Msx2 expression. In addition, EPA, ACSL3 siRNA and ACS inhibitor attenuated calcium deposition and caspase activation induced by PA. Notably, PA induced activation of NF-κB, and NF-κB inhibitor prevented PA-induction of osteoblastic gene expression and calcium deposition. Immunohistochemistry revealed the prominent expression of ACSL3 in VSMC and macrophages in human non-calcifying and calcifying atherosclerotic plaques from the carotid arteries. These results identify ACSL3 and NF-κB as mediators of PA-induced osteoblastic differentiation and calcium deposition in VSMC and suggest that EPA prevents vascular calcification by inhibiting such a new molecular pathway elicited by PA.

Indexed as

AortaBone Morphogenetic Protein 2CalcinosisCalciumCarotid ArteriesCaspasesCell DifferentiationCells, CulturedCoenzyme A LigasesEicosapentaenoic AcidGene ExpressionHomeodomain ProteinsHumansLong-Chain-Fatty-Acid-CoA LigaseMacrophagesMuscle, Smooth, VascularBMP2 protein, humanBone Morphogenetic Protein 2CalciumCaspasesCoenzyme A LigasesEicosapentaenoic AcidHomeodomain ProteinsLong-Chain-Fatty-Acid-CoA LigaseMSX2 proteinNF-kappa BOsteopontinPalmitic Acid

Identifiers

PMID23840832
PMCPMC3695932
OpenAlexW2146494263

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.