Evidence map›Paper›PMID 25110901›Full record

ReviewCurrent opinion in lipidology2014

PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells.

Thomas A Lagace

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

Review in Current opinion in lipidology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 187 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
187citing papers in PubMed, 6 pooled it
14.7field-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

187 citing papers in PubMed, 6 syntheses or guidelines pooled it, 353 citations in OpenAlex.

  1. Pooled it
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  11. Review
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  16. Are RNA Therapies a Solid Foundation or a Frontier Yet to Be Conquered?International journal of molecular sciences · 2026
    Review
  17. Article
  18. Review
  19. Enzyme-Assisted Synthesis and In Vitro Characterization of Bifunctional PCSK9 Inhibitors.Chembiochem : a European journal of chemical biology · 2026
    Article
  20. Review

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

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

1 author at 1 institution in 1 country.

Thomas A LagaceDepartment of Pathology and Laboratory Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
University of Ottawa · CA

Funding

Canadian Institutes of Health Research MOP 106462
6 · The paper itself

Abstract

purpose of reviewProprotein convertase subtilisin/kexin type-9 (PCSK9) binds to LDL receptor (LDLR) and targets it for lysosomal degradation in cells. Decreased hepatic clearance of plasma LDL-cholesterol is the primary gauge of PCSK9 activity in humans; however, PCSK9's evolutionary role may extend to other lipoprotein classes and processes. This review highlights studies that are providing novel insights into physiological regulation of PCSK9 transcription and plasma PCSK9 activity. RECENT

findingsRecent studies indicate that circulating PCSK9 binds to apolipoprotein B100 on LDL particles, which in turn inhibits PCSK9's ability to bind to cell surface LDLRs. Negative feedback of secreted PCSK9 activity by LDL could serve to increase plasma excursion of triglyceride-rich lipoproteins and monitor lipoprotein remodeling. Recent findings have identified hepatocyte nuclear factor-1α as a key transcriptional regulator that cooperates with sterol regulatory element-binding protein-2 to control PCSK9 expression in hepatocytes in response to nutritional and hormonal inputs, as well as acute inflammation. SUMMARY: PCSK9 is an established target for cholesterol-lowering therapies. Further study of PCSK9 regulatory mechanisms may identify additional control points for pharmacological inhibition of PCSK9-mediated LDLR degradation. PCSK9 function could reflect ancient roles in the fasting-feeding cycle and in linking lipoprotein metabolism with innate immunity.

Indexed as

Apolipoproteins BGene Expression RegulationHepatocytesHumansImmunity, InnateInflammationLipoproteins, LDLLysosomesProprotein Convertase 9Proprotein ConvertasesProtein BindingProteolysisReceptors, LDLSerine EndopeptidasesApolipoproteins BLDLR protein, humanLipoproteins, LDLPCSK9 protein, humanProprotein Convertase 9Proprotein ConvertasesReceptors, LDLSerine Endopeptidases

Identifiers

PMID25110901
PMCPMC4166010
OpenAlexW2036304437

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.