Evidence map›Paper›PMID 24969776›Full record

Trial reportArteriosclerosis, thrombosis, and vascular biology2014

CSL112 enhances biomarkers of reverse cholesterol transport after single and multiple infusions in healthy subjects.

Andreas Gille, Rachael Easton, Denise D'Andrea, Samuel D Wright, Charles L Shear

Open access · bronzeAbstract readComparative StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
13.5field-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

60 citing papers in PubMed, 112 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Andreas GilleFrom CSL Limited, Parkville, Victoria, Australia (A.G.); and CSL Behring, King of Prussia, PA (R.E., D.D., S.D.W., C.L.S.). andreas.gille@csl.com.au.
Rachael EastonFrom CSL Limited, Parkville, Victoria, Australia (A.G.); and CSL Behring, King of Prussia, PA (R.E., D.D., S.D.W., C.L.S.).
Denise D'AndreaFrom CSL Limited, Parkville, Victoria, Australia (A.G.); and CSL Behring, King of Prussia, PA (R.E., D.D., S.D.W., C.L.S.).
Samuel D WrightFrom CSL Limited, Parkville, Victoria, Australia (A.G.); and CSL Behring, King of Prussia, PA (R.E., D.D., S.D.W., C.L.S.).
Charles L ShearFrom CSL Limited, Parkville, Victoria, Australia (A.G.); and CSL Behring, King of Prussia, PA (R.E., D.D., S.D.W., C.L.S.).
CSL (Australia) · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThe ability of apolipoprotein A-I (apoA-I) to transport cholesterol from atherosclerotic plaque is thought to underlie its inverse correlation with cardiovascular risk. To gauge the potential of infused apoA-I to transport cholesterol, we quantified cholesterol transport markers in human subjects infused with a novel formulation of apoA-I (CSL112). APPROACH AND

resultsCSL112 was infused into human subjects in single (57 subjects) and multiple (36 subjects) ascending dose trials. Pharmacokinetic and biomarker assessments were conducted before and after infusions. CSL112 caused an immediate, up to 3-fold elevation of apoA-I and subsequent movement of tissue cholesterol into plasma. Cholesterol appeared first as unesterified cholesterol in the high-density lipoprotein (HDL) fraction and was promptly esterified by lecithin cholesterol acyltransferase. HDL cholesterol increased up to 81±16.5%. Underlying this movement of cholesterol was an immediate and strong rise in the ability of plasma to promote cholesterol efflux from cells ex vivo. CSL112 had its greatest impact on the fraction of efflux mediated by ATP-binding cassette transporter A1 (ABCA1), a cholesterol transporter induced in cholesterol-loaded tissues such as plaque. ABCA1-dependent efflux capacity increased ≤630±421% and total efflux capacity by ≤192±40%. In keeping with this finding, we observed a profound rise in very small HDL, also known as preβ1-HDL, the preferred substrate for ABCA1. Very small HDL increased ≤3596±941%. Elevations in apoA-I, cholesterol efflux, and very small HDL were dose-proportional over a wide range. No significant changes in atherogenic lipids were observed at any dose.

conclusionsInfusion of CSL112 elevates the ability of plasma to withdraw cholesterol from cells. Preferential elevation of ABCA1-dependent efflux may target atherosclerotic plaque for cholesterol removal, making CSL112 a promising candidate therapy for acute coronary syndrome.

Indexed as

AdultApolipoprotein A-IATP Binding Cassette Transporter 1Biological TransportBiomarkersCholesterolCholesterol EstersCholesterol, HDLDose-Response Relationship, DrugFemaleHumansInfusions, IntravenousLipoproteins, HDLMalePhosphatidylcholine-Sterol O-AcyltransferaseYoung AdultABCA1 protein, humanApolipoprotein A-IATP Binding Cassette Transporter 1BiomarkersCholesterolCholesterol EstersCholesterol, HDLCSL112Lipoproteins, HDLPhosphatidylcholine-Sterol O-Acyltransferaseacute coronary syndromeCSL112reverse cholesterol transport

Identifiers

PMID24969776
OpenAlexW2008062676

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.