Evidence map›Paper›PMID 29209441›Full record

ReviewThe EPMA journal2017

PCSK9 signaling pathways and their potential importance in clinical practice.

Michał Wiciński, Jarosław Żak, Bartosz Malinowski, Gabriela Popek, Grzegorz Grześk

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

Review in The EPMA journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
4.2field-weighted citation impact, top 6% 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

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 66 citations in OpenAlex.

  1. Lipid homeostasis in diabetic kidney disease.International journal of biological sciences · 2024
    Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Protein Kinases in Obesity, and the Kinase-Targeted Therapy.Advances in experimental medicine and biology · 2024
    Review
  19. Article
  20. Review
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

5 authors at 2 institutions in 1 country.

Michał WicińskiDepartment of Pharmacology and Therapeutics, Faculty of Medicine, Collegium, Medicum in Bydgoszcz, Nicolaus Copernicus University, 85-090 Bydgoszcz, Poland.
Jarosław ŻakDepartment of Pharmacology and Therapeutics, Faculty of Medicine, Collegium, Medicum in Bydgoszcz, Nicolaus Copernicus University, 85-090 Bydgoszcz, Poland.
Bartosz MalinowskiDepartment of Pharmacology and Therapeutics, Faculty of Medicine, Collegium, Medicum in Bydgoszcz, Nicolaus Copernicus University, 85-090 Bydgoszcz, Poland.
Gabriela PopekDepartment of Pharmacology and Therapeutics, Faculty of Medicine, Collegium, Medicum in Bydgoszcz, Nicolaus Copernicus University, 85-090 Bydgoszcz, Poland.
Grzegorz GrześkDepartment of Pharmacology and Therapeutics, Faculty of Medicine, Collegium, Medicum in Bydgoszcz, Nicolaus Copernicus University, 85-090 Bydgoszcz, Poland.
Nicolaus Copernicus University · PLCollegium Medicum in Bydgoszcz · PL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In the following review, authors described the structure and biochemical pathways of PCSK9, its involvement in LDL metabolism, as well as significances of proprotein convertase subtilisin/kexin type 9 targeted treatment. PCSK9 is a proprotein convertase, which plays a crucial role in LDL receptor metabolism. Transcription and translation of PCSK9 is controlled by different nuclear factors, such as, SREBP and HNF1α. This review focuses on interactions between PCSK9 and LDL receptor, VLDLR, ApoER2, CD36, CD81, and others. The role of PCSK9 in the inflammatory process is presented and its influence on cytokine profile (IL-1, IL-6, IL-10, TNF) in atherosclerotic plaque. Cholesterol metabolism converges also with diabetes by mTORC1 pathways. PCSK9 can be altered by oncologic pathways with utilization of kinases, such as Akt, JNK, and JAK/STAT. Finally, the article shows that blocking PCSK9 has proapoptotic capabilities. Administration of monoclonal antibodies against PCSK9 reduced mortality rate and cardiovascular events in randomized trials. On the other hand, immunogenicity of new drugs may play a crucial role in their efficiency. Bococizumab ended its career following SPIRE-1,2 outcome. PCSK9 inhibitors have enormous potential, which had been reflected by introducing them (as a new class of drugs reducing LDL concentration cholesterol) into New Lipid Guidelines from Rome 2016. Discoveries in drugs development are focused on blocking PCSK9 on different levels. For example, silencing messenger RNA (mRNA of PCSK9) is a new alternative against hypercholesterolemia. Peptides mimicking EGF-A domain of the LDL receptor are gaining significance and hopefully they will soon join others. The significance of PCSK9 has just been uncovered and further data is still required to understand their activity.

Indexed as

ApoptosisCell signalingInflammationLDLMetabolismPCSK9

Identifiers

PMID29209441
PMCPMC5700013
OpenAlexW2746291808

What OpenQuestion 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 OpenQuestion graph.