Evidence map›Paper›PMID 40853922›Full record

ArticleCardiovascular research2025

Eicosapentaenoic acid limits the more rapid oxidation of lipoprotein(a) compared with other apolipoprotein B particles.

Samuel C R Sherratt, Peter Libby, Richard L Dunbar, Deepak L Bhatt, R Preston Mason

Abstract readComparative Study
In one paragraph

Article in Cardiovascular research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Samuel C R SherrattMount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA.ORCID 0000-0002-0913-2865
Peter LibbyDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA.ORCID 0000-0002-1502-502X
Richard L DunbarAmarin Pharma, Inc., 440 Route 22 East, Suite 300, Bridgewater, NJ 08807, USA.ORCID 0000-0002-7059-4794
Deepak L BhattMount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA.ORCID 0000-0002-1278-6245
R Preston MasonElucida Research, 100 Cummings Center, Suite 135L, Beverly, MA 01915, USA.ORCID 0000-0001-5483-1852

Funding

Amarin Pharma Inc.Elucida Research LLC
6 · The paper itself

Abstract

aimsElevated lipoprotein(a) [Lp(a)] levels increase cardiovascular (CV) risk. Lp(a) contains oxidized phospholipids that may promote lipid oxidation more than other lipoproteins. The highly unsaturated omega-3 fatty acid eicosapentaenoic acid (EPA) has multiple double bonds that can trap free radicals in resonance structures. Purified ethyl-EPA reduced CV events in high-risk patients with elevated Lp(a) despite Lp(a)-associated risk elevation. Since Lp(a) is enriched in oxidized lipids, we hypothesized that Lp(a)-enriched plasma undergoes more rapid oxidation than other apolipoprotein B (ApoB)-containing particles and that EPA limits oxidation of Lp(a)-enriched plasma more effectively than less-unsaturated fatty acids or other lipid-lowering treatments. This property could limit the cellular stress responses in endothelial cells (ECs). METHODS AND

resultsLp(a) was enriched to >50% total ApoB content to resemble an Lp(a)-associated 'high-risk' phenotype and compared with matching levels of small-dense LDL (sdLDL) and very-low-density lipoprotein by isopycnic centrifugation. Samples were then incubated with EPA (50 µM) or equivolume vehicle at 37°C for 30 min. Oxidation was initiated with copper sulfate and monitored by malondialdehyde formation. We also subjected EPA to oxidation before measuring its antioxidant activity when compared with other long chain, less saturated fatty acids and lipid-lowering agents. Human umbilical vein ECs (HUVECs) were incubated with Lp(a)-enriched plasma following oxidation in the absence and presence of EPA. Cell lysate samples were then analysed by global liquid chromatography-mass spectroscopy (LC/MS)-based proteomics for significant changes in protein expression (>1-fold). Lp(a)-enriched plasma contained the highest baseline oxidized lipid (P < 0.05) and underwent the most rapid oxidation. EPA, but neither the less-unsaturated fatty acids nor lipid agents attenuated oxidation of each fraction through 4 h (P < 0.01). Oxidized EPA had diminished antioxidant capacity corresponding to the extent of oxidation. Attenuation of Lp(a) oxidation with EPA also mitigated pro-inflammatory and cellular stress response changes in protein expression.

conclusionsLp(a)-enriched plasma underwent more rapid oxidation than other ApoB-containing lipoproteins and promoted inflammatory changes in EC protein expression, a process attenuated by EPA. This action may contribute to reduced CV risk by EPA in those with elevated Lp(a) levels.

Indexed as

AntioxidantsEicosapentaenoic AcidHuman Umbilical Vein Endothelial CellsLipoprotein(a)Apolipoprotein B-100Cells, CulturedHumansOxidation-ReductionOxidative StressTime FactorsAntioxidantsAPOB protein, humanApolipoprotein B-100Eicosapentaenoic AcidLipoprotein(a)Eicosapentaenoic acidLipoprotein(a)Oxidation

Identifiers

PMID40853922
PMCPMC12560759

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.