Evidence map›Paper›PMID 24625727›Full record

ReviewCirculation research2014

PCSK9: a key modulator of cardiovascular health.

Nabil G Seidah, Zuhier Awan, Michel Chrétien, Majambu Mbikay

2 registry-linked trialsOpen access · bronzeAbstract readReview
PubMed Publisher
In one paragraph

Review in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 268 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
268citing papers in PubMed, 4 pooled it
56.3field-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.

NCT04338165 phase2unknown statusstarted 2021, after this paper: background citation

Effect of Impact of PCSK9 Inhibitors on Coronary Microvascular Dysfunction in Patients With Atherosclerotic Cardiovascular Disease Proved by Myocardial Ischemia and Needing Coronarography : a Monocentric, Prospective, Randomized and Open-label Phase II Trial

Ran2021Enrolled66Registered outcomes6Posted comparisons0ConditionsAtherosclerotic Cardiovascular DiseaseArmsEvolocumab 140 MG/ML [Repatha]
PMID 28304224PMID 29525934PMID 11074073PMID 23347861PMID 25400060PMID 25490141PMID 27222591PMID 27567407PMID 27846344PMID 28056463PMID 9396430PMID 30165437other papers from this trial
Open the trial in the graph
NCT03634293 phase2 / phase3unknown statusnot on this mapstarted 2019, after this paper: background citation

PCSK9 Inhibitor: a New Tool to Fight Septic Shock

TypeinterventionalSponsorWolfson Medical CenterRan2019 to 2021Enrolled712ConditionsSepsis, Septic ShockArmsAlirocumab Injectable Product, Saline Solution
3 · Its place in the literature

Who cites it

268 citing papers in PubMed, 4 syntheses or guidelines pooled it, 578 citations in OpenAlex.

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208 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

4 authors at 1 institution in 1 country.

Nabil G SeidahFrom the Laboratories of Biochemical Neuroendocrinology (N.G.S., Z.A.) and Functional Endoproteolysis (M.C., M.M.), Institut de Recherches Cliniques de Montréal, affiliated to the Université de Montréal, Montréal, Quebec, Canada; and Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada (M.C., M.M.).
Zuhier Awan
Michel Chrétien
Majambu Mbikay
Montreal Clinical Research Institute · CA

Funding

Canadian Institutes of Health Research MOP 102618Canadian Institutes of Health Research MOP 102741
6 · The paper itself

Abstract

Since the discovery of proprotein convertase subtilisin kexin 9 (PCSK9) in 2003, this PC has attracted a lot of attention from the scientific community and pharmaceutical companies. Secreted into the plasma by the liver, the proteinase K-like serine protease PCSK9 binds the low-density lipoprotein (LDL) receptor at the surface of hepatocytes, thereby preventing its recycling and enhancing its degradation in endosomes/lysosomes, resulting in reduced LDL-cholesterol clearance. Surprisingly, in a nonenzymatic fashion, PCSK9 enhances the intracellular degradation of all its target proteins. Rare gain-of-function PCSK9 variants lead to higher levels of LDL-cholesterol and increased risk of cardiovascular disease; more common loss-of-function PCSK9 variants are associated with reductions in both LDL-cholesterol and risk of cardiovascular disease. It took 9 years to elaborate powerful new PCSK9-based therapeutic approaches to reduce circulating levels of LDL-cholesterol. Presently, PCSK9 monoclonal antibodies that inhibit its function on the LDL receptor are evaluated in phase III clinical trials. This review will address the biochemical, genetic, and clinical aspects associated with PCSK9's biology and pathophysiology in cells, rodent and human, with emphasis on the clinical benefits of silencing the expression/activity of PCSK9 as a new modality in the treatment of hypercholesterolemia and associated pathologies.

Indexed as

AdultAgingAnimalsCardiovascular DiseasesChildCholesterol, LDLChromosomes, Human, Pair 1Clinical Trials, Phase III as TopicDietDisease Models, AnimalEndosomesFemaleGene Expression Regulation, EnzymologicGenetic Predisposition to DiseaseHepatitis CHepatocytesCholesterol, LDLLipoproteins, LDLLow Density Lipoprotein Receptor-Related Protein-1PCSK9 protein, humanProprotein Convertase 9Proprotein ConvertasesReceptors, LDLSerine EndopeptidasesVLDL receptorclinical trials, phase III as topichyperlipoproteinemia type IILDL cholesterol

Identifiers

PMID24625727
OpenAlexW2099654648

What OpenQuestion holds

Texttitle and abstract
Read underepoch 390

Registered trials

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.