Evidence map›Paper›PMID 22611251›Full record

ArticleJournal of lipid research2012

Immunization against proprotein convertase subtilisin-like/kexin type 9 lowers plasma LDL-cholesterol levels in mice.

Elena Fattori, Manuela Cappelletti, Paola Lo Surdo, Alessandra Calzetta, Claus Bendtsen, Yan G Ni, Shilpa Pandit, Ayesha Sitlani, Giuseppe Mesiti, Andrea Carfí and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of lipid research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

19 citing papers in PubMed, 35 citations in OpenAlex.

  1. Engineering chimeric PCSK9 for a vaccine against atherosclerosis.Molecular therapy. Methods & clinical development · 2025
    Article
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  3. Dyslipidemia: A Narrative Review on Pharmacotherapy.Pharmaceuticals (Basel, Switzerland) · 2024
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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

11 authors at 2 institutions in 2 countries.

Elena FattoriBiotechnology Department, Istituto di Ricerche di Biologia Molecolare P. Angeletti, I-00040 Pomezia (Roma), Italy.
Manuela Cappelletti
Paola Lo Surdo
Alessandra Calzetta
Claus Bendtsen
Yan G Ni
Shilpa Pandit
Ayesha Sitlani
Giuseppe Mesiti
Andrea Carfí
Paolo Monaci
Istituto di Genetica Molecolare · ITMerck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Successful development of drugs against novel targets crucially depends on reliable identification of the activity of the target gene product in vivo and a clear demonstration of its specific functional role for disease development. Here, we describe an immunological knockdown (IKD) method, a novel approach for the in vivo validation and functional study of endogenous gene products. This method relies on the ability to elicit a transient humoral response against the selected endogenous target protein. Anti-target antibodies specifically bind to the target protein and a fraction of them effectively neutralize its activity. We applied the IKD method to the in vivo validation of plasma PCSK9 as a potential target for the treatment of elevated levels of plasma LDL-cholesterol. We show that immunization with human-PCSK9 in mice is able to raise antibodies that cross-react and neutralize circulating mouse-PCSK9 protein thus resulting in increased liver LDL receptor levels and plasma cholesterol uptake. These findings closely resemble those described in PCSK9 knockout mice or in mice treated with antibodies that inhibit PCSK9 by preventing the PCSK9/LDLR interaction. Our data support the IKD approach as an effective method to the rapid validation of new target proteins.

Indexed as

ImmunizationAnimalsAntibodiesCholesterol, LDLFemaleHEK293 CellsHumansLiverMiceProprotein Convertase 9Proprotein ConvertasesReceptors, LDLSerine EndopeptidasesAntibodiesCholesterol, LDLPcsk9 protein, mouseProprotein Convertase 9Proprotein ConvertasesReceptors, LDLSerine Endopeptidases

Identifiers

PMID22611251
PMCPMC3540849
OpenAlexW2149383594

What OpenQuestion holds

Textmetadata
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.