Evidence map›Paper›PMID 25143462›Full record

ArticleJournal of lipid research2014

Atheroprotective immunization with malondialdehyde-modified LDL is hapten specific and dependent on advanced MDA adducts: implications for development of an atheroprotective vaccine.

Ayelet Gonen, Lotte F Hansen, William W Turner, Erica N Montano, Xuchu Que, Apaїs Rafia, Meng-Yun Chou, Philipp Wiesner, Dimitrios Tsiantoulas, Maripat Corr and 5 more

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

Article in Journal of lipid research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.0field-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

36 citing papers in PubMed, 51 citations in OpenAlex.

  1. Trial
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  7. Atherosclerosis antigens as targets for immunotherapy.Nature cardiovascular research · 2023
    Review
  8. Human circulating CD24Nature cardiovascular research · 2023
    Article
  9. Article
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  12. The OSE complotype and its clinical potential.Frontiers in immunology · 2022
    Review
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  16. Article
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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

15 authors at 3 institutions in 3 countries.

Ayelet GonenDepartment of Medicine, University of California, San Diego, La Jolla, CA.
Lotte F HansenDepartment of Medicine, University of California, San Diego, La Jolla, CA.
William W TurnerDepartment of Chemistry, Indiana University, Bloomington, IN.
Erica N MontanoDepartment of Medicine, University of California, San Diego, La Jolla, CA.
Xuchu QueDepartment of Medicine, University of California, San Diego, La Jolla, CA.
Apaїs RafiaDepartment of Medicine, University of California, San Diego, La Jolla, CA.
Meng-Yun ChouDepartment of Medicine, University of California, San Diego, La Jolla, CA.
Philipp WiesnerDepartment of Medicine, University of California, San Diego, La Jolla, CA.
Dimitrios TsiantoulasDepartment of Laboratory Medicine, Medical University of Vienna, Vienna, Austria Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria.
Maripat CorrDepartment of Medicine, University of California, San Diego, La Jolla, CA.
Michael S VanNieuwenhzeDepartment of Chemistry, Indiana University, Bloomington, IN.
Sotirios TsimikasDepartment of Medicine, University of California, San Diego, La Jolla, CA.
Christoph J BinderDepartment of Medicine, University of California, San Diego, La Jolla, CA Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria Center for Molecular Medicine (CeMM) of the Austrian Academy of Sciences, Vienna, Austria.
Joseph L WitztumDepartment of Medicine, University of California, San Diego, La Jolla, CA.
Karsten HartvigsenDepartment of Medicine, University of California, San Diego, La Jolla, CA Department of Biomedical Sciences, University of Copenhagen, Denmark.
University of California, San Diego · USIndiana University Bloomington · USMedical University of Vienna · AT

Funding

Transcriptional GenomicsP01HL088093 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WITZTUM, JOSEPH L. · 2008 to 2018
$26.4M
Development of a Vaccine Approach to Inhibit AtherosclerosisR01HL086559 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WITZTUM, JOSEPH L. · 2007 to 2011
$2.0M
NHLBI NIH HHS HL086559NHLBI NIH HHS HL088093NHLBI NIH HHS P01 HL088093NHLBI NIH HHS R01 HL086559
6 · The paper itself

Abstract

Immunization with homologous malondialdehyde (MDA)-modified LDL (MDA-LDL) leads to atheroprotection in experimental models supporting the concept that a vaccine to oxidation-specific epitopes (OSEs) of oxidized LDL could limit atherogenesis. However, modification of human LDL with OSE to use as an immunogen would be impractical for generalized use. Furthermore, when MDA is used to modify LDL, a wide variety of related MDA adducts are formed, both simple and more complex. To define the relevant epitopes that would reproduce the atheroprotective effects of immunization with MDA-LDL, we sought to determine the responsible immunodominant and atheroprotective adducts. We now demonstrate that fluorescent adducts of MDA involving the condensation of two or more MDA molecules with lysine to form malondialdehyde-acetaldehyde (MAA)-type adducts generate immunodominant epitopes that lead to atheroprotective responses. We further demonstrate that a T helper (Th) 2-biased hapten-specific humoral and cellular response is sufficient, and thus, MAA-modified homologous albumin is an equally effective immunogen. We further show that such Th2-biased humoral responses per se are not atheroprotective if they do not target relevant antigens. These data demonstrate the feasibility of development of a small-molecule immunogen that could stimulate MAA-specific immune responses, which could be used to develop a vaccine approach to retard or prevent atherogenesis.

Indexed as

AtherosclerosisHaptensImmunizationLipoproteins, LDLMalondialdehydeVaccinesAnimalsHumansImmunity, CellularImmunity, HumoralMaleMiceMice, KnockoutTh2 CellsHaptensLipoproteins, LDLMalondialdehydeVaccinesadaptive immunityhumoral immunitymalondialdehyde-acetaldehyde adductsoxidation-specific epitopes

Identifiers

PMID25143462
PMCPMC4174006
OpenAlexW1977878140

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.