Evidence map›Paper›PMID 23613182›Full record

ArticleCirculation research2013

Pegylation of high-density lipoprotein decreases plasma clearance and enhances antiatherogenic activity.

Andrew J Murphy, Samuel Funt, Darren Gorman, Alan R Tall, Nan Wang

Open access · bronzeAbstract read
In one paragraph

Article in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

24 citing papers in PubMed, 56 citations in OpenAlex.

  1. Trial
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  6. Addressing dyslipidemic risk beyond LDL-cholesterol.The Journal of clinical investigation · 2022
    Review
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  19. Cholesterol, inflammation and innate immunity.Nature reviews. Immunology · 2015 · on this map
    Review
  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

5 authors at 1 institution in 1 country.

Andrew J MurphyDivision of Molecular Medicine, Department of Medicine, Columbia University, New York, New York 10032, USA.
Samuel FuntDivision of Molecular Medicine, Department of Medicine, Columbia University, New York, New York 10032, USA.
Darren GormanDivision of Molecular Medicine, Department of Medicine, Columbia University, New York, New York 10032, USA.
Alan R Tall *Division of Molecular Medicine, Department of Medicine, Columbia University, New York, New York 10032, USA.
Nan Wang *Division of Molecular Medicine, Department of Medicine, Columbia University, New York, New York 10032, USA.
Columbia University · US

Funding

TTC39B in obesity and atherosclerosisP01HL087123 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI TALL, ALAN RICHARD · 2007 to 2022
$31.2M
Cholesterol efflux, CHIP and inflammasome activationR01HL107653 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ALAN richard TALL · 2011 to 2026
$7.7M
NHLBI NIH HHS HL107653NHLBI NIH HHS HL87123NHLBI NIH HHS P01 HL087123NHLBI NIH HHS R01 HL107653
6 · The paper itself

Abstract

rationaleInfusions of apolipoprotein AI (apoAI), mimetic peptides, or high-density lipoprotein (HDL) remain a promising approach for the treatment of atherosclerotic coronary disease. However, rapid clearance leads to a requirement for repeated administration of large amounts of material and limits effective plasma concentrations.

objectiveBecause pegylation of purified proteins is commonly used as a method to increase their half-life in the circulation, we determined whether pegylation of apoAI or HDL would increase its plasma half-life and in turn its antiatherogenic potential. METHODS AND

resultsInitial pegylation attempts using lipid-poor apoAI showed a marked tendency to form multi-pegylated (PEG) species with reduced ability to promote cholesterol efflux from macrophage foam cells. However, pegylation of human holo-HDL or reconstituted phospholipid/apoAI particles (rHDL) led to selective N-terminal monopegylation of apoAI with full preservation of cholesterol efflux activity. The plasma clearance of PEG-rHDL was estimated after injection into hypercholesterolemic Apoe-/- mice; the half-life of pegylated PEG-apoAI after injection of PEG-rHDL was increased ≈7-fold compared with apoAI in nonpegylated rHDL. In comparison with nonpegylated rHDL, infusion of PEG-rHDL (40 mg/kg) into hypercholesterolemic Apoe-/- mice led to more pronounced suppression of bone marrow myeloid progenitor cell proliferation and monocytosis, as well as reduced atherosclerosis and a stable plaque phenotype.

conclusionsWe describe a novel method for effective monopegylation of apoAI in HDL particles, in which lipid binding seems to protect against pegylation of key functional residues. Pegylation of apoAI in rHDL markedly increases its plasma half-life and enhances antiatherogenic properties in vivo.

Indexed as

AnimalsAortic DiseasesApolipoprotein A-IApolipoproteins EAtherosclerosisCell LineCholesterolDrug Evaluation, PreclinicalFoam CellsHalf-LifeHematopoietic Stem CellsHumansHypercholesterolemiaInfusions, IntravenousInjections, IntravenousLipoproteins, HDLApolipoprotein A-IApolipoproteins ECholesterolLipoproteins, HDLPolyethylene GlycolsapoAIatherosclerosischolesterolHDLhematopoiesis

Identifiers

PMID23613182
PMCPMC3905798
OpenAlexW2215181089

What OpenQuestion holds

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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.