Evidence map›Paper›PMID 26474593›Full record

ArticleJournal of lipid research2015

Mechanistic insights into Lp(a)-induced IL-8 expression: a role for oxidized phospholipid modification of apo(a).

Corey A Scipione, Sera E Sayegh, Rocco Romagnuolo, Sotirios Tsimikas, Santica M Marcovina, Michael B Boffa, Marlys L Koschinsky

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

Article in Journal of lipid research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
9.1field-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

52 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.

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  16. Lipoprotein(a) and cardiovascular disease.The Biochemical journal · 2024
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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

7 authors at 3 institutions in 2 countries.

Corey A ScipioneDepartment of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada.
Sera E SayeghDepartment of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada.
Rocco RomagnuoloDepartment of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada.
Sotirios TsimikasVascular Medicine Program, University of California San Diego, La Jolla, CA.
Santica M MarcovinaDepartment of Medicine, Northwest Lipid Research Laboratories, University of Washington, Seattle, WA.
Michael B BoffaDepartment of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada.
Marlys L KoschinskyDepartment of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada mlk@robarts.ca.
University of Windsor · CAUniversity of California, San Diego · USUniversity of Washington · US

Funding

Canadian Institutes of Health Research 126076
6 · The paper itself

Abstract

Elevated lipoprotein (a) [Lp(a)] levels are a causal risk factor for coronary heart disease. Accumulating evidence suggests that Lp(a) can stimulate cellular inflammatory responses through the kringle-containing apolipoprotein (a) [apo(a)] component. Here, we report that recombinant apo(a) containing 17 kringle (17K) IV domains elicits a dose-dependent increase in interleukin (IL)-8 mRNA and protein expression in THP-1 and U937 macrophages. This effect was blunted by mutation of the lysine binding site in apo(a) kringle IV type 10, which resulted in the loss of oxidized phospholipid (oxPL) on apo(a). Trypsin-digested 17K had the same stimulatory effect on IL-8 expression as intact apo(a), while enzymatic removal of oxPL from apo(a) significantly blunted this effect. Using siRNA to assess candidate receptors, we found that CD36 and TLR2 may play roles in apo(a)-mediated IL-8 stimulation. Downstream of these receptors, inhibitors of MAPKs, Jun N-terminal kinase and ERK1/2, abolished the effect of apo(a) on IL-8 gene expression. To assess the roles of downstream transcription factors, luciferase reporter gene experiments were conducted using an IL-8 promoter fragment. The apo(a)-induced expression of this reporter construct was eliminated by mutation of IL-8 promoter binding sites for either NF-κB or AP-1. Our results provide a mechanistic link between oxPL modification of apo(a) and stimulation of proinflammatory intracellular signaling pathways.

Indexed as

ApolipoproteinsApolipoproteins ABinding SitesCell LineHumansInterleukin-8NF-kappa BPhospholipidsRNA, Small InterferingTranscription Factor AP-1ApolipoproteinsApolipoproteins ACXCL8 protein, humanInterleukin-8NF-kappa BPhospholipidsRNA, Small InterferingTranscription Factor AP-1apolipoprotein (a)atherosclerosisinflammationinterleukin-8lipoprotein (a)

Identifiers

PMID26474593
PMCPMC4655984
OpenAlexW2189713131

What OpenQuestion holds

Textmetadata
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.