Evidence map›Paper›PMID 29438441›Full record

ArticlePloS one2018

Development of vaccine for dyslipidemia targeted to a proprotein convertase subtilisin/kexin type 9 (PCSK9) epitope in mice.

Ryo Kawakami, Yoichi Nozato, Hironori Nakagami, Yuka Ikeda, Munehisa Shimamura, Shota Yoshida, Jiao Sun, Tomohiro Kawano, Yoichi Takami, Takahisa Noma and 3 more

Open access · goldFull text read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 3% 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

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Dyslipidemia: A Narrative Review on Pharmacotherapy.Pharmaceuticals (Basel, Switzerland) · 2024
    Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  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

13 authors at 2 institutions in 1 country.

Ryo KawakamiDepartment of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Yoichi NozatoDepartment of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Hironori NakagamiDepartment of Health Development and Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.ORCID 0000-0003-4494-3601
Yuka IkedaDepartment of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Munehisa ShimamuraDepartment of Health Development and Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Shota YoshidaDepartment of Health Development and Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Jiao SunDepartment of Health Development and Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Tomohiro KawanoDepartment of Neurology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Yoichi TakamiDepartment of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Takahisa NomaDepartment of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Hiromi RakugiDepartment of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Tetsuo MinaminoDepartment of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
Ryuichi MorishitaDepartment of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
The University of Osaka · JPKagawa University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates expression of low-density lipoprotein (LDL) receptors via receptor internalization and subsequent lysosomal degradation. Thus, an anti-PCSK9 antibody is well known as an anti-hyperlipidemia drug. Here, we aimed to develop vaccine for a long-term treatment of dyslipidemia targeted to PCSK9. In This study, we designed a peptide vaccine for mouse PCSK-9, which consisted of short peptides conjugated to keyhole limpet hemocyanin (KLH) as a carrier protein. Vaccines were administered to male apolipoprotein E (ApoE) deficient mice with adjuvants and significantly elicited an antibody response against PCSK9. The PCSK9 vaccines were administered to mice three times in 2-week intervals, and antibody titers and lipoprotein levels were evaluated up to 24 weeks after the first immunization to determine the therapeutic effect. Anti-PCSK9 antibody titers reached peak levels 6 weeks after the first immunization, and theses titers were maintained for up to 24 weeks. Decreased plasma levels of total cholesterol, very low-density lipoprotein (VLDL), and chylomicron (CM) were maintained for up to 24 weeks. Immunized mice exhibited a significant increase in cell-surface LDL receptor expression. Stimulation with KLH, but not PCSK9, induced the production of INF-gamma and interleukin-4 (IL-4), as determined with ELISPOT assays, thus indicating that PCSK9 vaccine did not elicit T-cell activation in our vaccine system. The present anti-PCSK9 vaccine induced long-lasting anti-PCSK9 antibody production and improved lipoprotein profiles. Thus, anti-PCSK9 vaccine could become a new option for the treatment of dyslipidemia as a long-acting therapy in future.

Indexed as

AnimalsDyslipidemiasEnzyme-Linked Immunosorbent AssayMiceProprotein Convertase 9VaccinesPcsk9 protein, mouseProprotein Convertase 9Vaccines

Identifiers

PMID29438441
PMCPMC5811007
OpenAlexW2794320485

What Socratic holds

Textfull text, public
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.