Evidence map›Paper›PMID 28637178›Full record

ArticleEuropean heart journal2017

The AT04A vaccine against proprotein convertase subtilisin/kexin type 9 reduces total cholesterol, vascular inflammation, and atherosclerosis in APOE*3Leiden.CETP mice.

Christine Landlinger, Marianne G Pouwer, Claudia Juno, José W A van der Hoorn, Elsbet J Pieterman, J Wouter Jukema, Guenther Staffler, Hans M G Princen, Gergana Galabova

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

Article in European heart journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
118citing papers in PubMed, 4 pooled it
24.6field-weighted citation impact, top 1% 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

118 citing papers in PubMed, 4 syntheses or guidelines pooled it, 220 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Biotechnology Approaches for the Treatment of Dyslipidemia.Cardiovascular drugs and therapy · 2021
    Pooled it
  4. Pooled it
  5. Trial
  6. Trial
  7. Nanomaterials-Based Immunotherapy for Atherosclerosis.Small (Weinheim an der Bergstrasse, Germany) · 2026
    Review
  8. Article
  9. Article
  10. Review
  11. PCSK9 in critical illness - It's not all about lipids.Annals of clinical biochemistry · 2026
    Review
  12. Article
  13. Review
  14. Article
  15. Contribution of Gli1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. Mitigating atherosclerosis: Integrating vaccines with gene targets.American heart journal plus : cardiology research and practice · 2025
    Review

58 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Christine LandlingerAFFiRiS AG, Karl-Farkas-Gasse 22, Vienna 1030, Austria.
Marianne G PouwerDepartment of Cardiology, LUMC, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Claudia JunoAFFiRiS AG, Karl-Farkas-Gasse 22, Vienna 1030, Austria.
José W A van der HoornThe Netherlands Organization of Applied Scientific Research (TNO)-Metabolic Health Research, Gaubius Laboratory, Zernikedreef 9, 2333 CK, PO Box 2215, 2301CE, Leiden, The Netherlands.
Elsbet J PietermanThe Netherlands Organization of Applied Scientific Research (TNO)-Metabolic Health Research, Gaubius Laboratory, Zernikedreef 9, 2333 CK, PO Box 2215, 2301CE, Leiden, The Netherlands.
J Wouter JukemaDepartment of Cardiology, LUMC, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Guenther StafflerAFFiRiS AG, Karl-Farkas-Gasse 22, Vienna 1030, Austria.
Hans M G PrincenThe Netherlands Organization of Applied Scientific Research (TNO)-Metabolic Health Research, Gaubius Laboratory, Zernikedreef 9, 2333 CK, PO Box 2215, 2301CE, Leiden, The Netherlands.
Gergana GalabovaAFFiRiS AG, Karl-Farkas-Gasse 22, Vienna 1030, Austria.
AFFiRiS (Austria) · ATNetherlands Organisation for Applied Scientific Research · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsProprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target for the treatment of hypercholesterolaemia and atherosclerosis. PCSK9 binds to the low density lipoprotein receptor and enhances its degradation, which leads to the reduced clearance of low density lipoprotein cholesterol (LDLc) and a higher risk of atherosclerosis. In this study, the AT04A anti-PCSK9 vaccine was evaluated for its therapeutic potential in ameliorating or even preventing coronary heart disease in the atherogenic APOE*3Leiden.CETP mouse model. METHODS AND

resultsControl and AT04A vaccine-treated mice were fed western-type diet for 18 weeks. Antibody titres, plasma lipids, and inflammatory markers were monitored by ELISA, FPLC, and multiplexed immunoassay, respectively. The progression of atherosclerosis was evaluated by histological analysis of serial cross-sections from the aortic sinus. The AT04A vaccine induced high and persistent antibody levels against PCSK9, causing a significant reduction in plasma total cholesterol (-53%, P < 0.001) and LDLc compared with controls. Plasma inflammatory markers such as serum amyloid A (SAA), macrophage inflammatory protein-1β (MIP-1β/CCL4), macrophage-derived chemokine (MDC/CCL22), cytokine stem cell factor (SCF), and vascular endothelial growth factor A (VEGF-A) were significantly diminished in AT04A-treated mice. As a consequence, treatment with the AT04A vaccine resulted in a decrease in atherosclerotic lesion area (-64%, P = 0.004) and aortic inflammation as well as in more lesion-free aortic segments (+119%, P = 0.026), compared with control.

conclusionsAT04A vaccine induces an effective immune response against PCSK9 in APOE*3Leiden.CETP mice, leading to a significant reduction of plasma lipids, systemic and vascular inflammation, and atherosclerotic lesions in the aorta.

Indexed as

PCSK9 InhibitorsAnimalsAntibodiesAortic DiseasesApolipoprotein E3AtherosclerosisBiomarkersCholesterol, HDLCoronary DiseaseDisease Models, AnimalFemaleHypercholesterolemiaIntercellular Adhesion Molecule-1Mice, TransgenicNLR Family, Pyrin Domain-Containing 3 ProteinPlaque, AtheroscleroticAntibodiesApolipoprotein E3AT04A vaccineBiomarkersCholesterol, HDLIntercellular Adhesion Molecule-1NLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mousePCSK9 InhibitorsPcsk9 protein, mouseProprotein Convertase 9Vaccines, SubunitAnti-PCSK9 vaccineAPOE*3Leiden.CETP miceAtherosclerosisSystemic and vascular inflammation

Identifiers

PMID28637178
PMCPMC5837708
OpenAlexW2654759377

What OpenQuestion holds

Texttitle and abstract
LicenceCC BY-NC
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.