Evidence map›Paper›PMID 18497309›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2008

Lentiviral transduction of apoAI into hematopoietic progenitor cells and macrophages: applications to cell therapy of atherosclerosis.

Yan Ru Su, John L Blakemore, Youmin Zhang, MacRae F Linton, Sergio Fazio

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

11 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Article
  3. Age, APOE and sex: Triad of risk of Alzheimer's disease.The Journal of steroid biochemistry and molecular biology · 2016
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Expression of apolipoprotein A-I in rabbit carotid endothelium protects against atherosclerosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2011
    Article
  9. Article
  10. Insights into atherosclerosis using nanotechnology.Current atherosclerosis reports · 2010
    Review
  11. 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.

Yan Ru SuDivision of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville TN 37232-6300, USA. yan.ru.su@vanderbilt.edu
John L Blakemore
Youmin Zhang
MacRae F Linton
Sergio Fazio
Vanderbilt University Medical Center · US

Funding

Vanderbilt Diabetes Research CenterP30DK020593 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI OWEN P MCGUINNESS · 2012 to 2026
$29.3M
TRANSGENIC MOUSE/ ES CELL SHARES RESOURCESP60DK020593 · NIDDK · VANDERBILT UNIVERSITY · PI MCGUINNESS, OWEN P · 1986 to 2011
$28.1M
FUNCTIONAL HIERARCHY OF REMNANT LIPOPROTEIN RECEPTORSR01HL057986 · NHLBI · VANDERBILT UNIVERSITY · PI FAZIO, SERGIO · 1998 to 2016
$6.2M
ROLE OF FATTY ACID BINDING PROTEINS IN ATHEROSCLEROSISR01HL065405 · NHLBI · VANDERBILT UNIVERSITY · PI LINTON, MACRAE F · 2000 to 2009
$4.0M
MACROPHAGE EXPRESSION OF APOAI AND ATHEROSCLEROSISR01HL065709 · NHLBI · VANDERBILT UNIVERSITY · PI FAZIO, SERGIO · 2000 to 2008
$3.2M
ApoE and SR-BI as Determinants of HDL and Macrophage Function in AtherogenesisR01HL086988 · NHLBI · VANDERBILT UNIVERSITY · PI LINTON, MACRAE F · 2007 to 2010
$1.5M
BONE MARROW TRANSPLANTION AND ATHEROSCLEROSISR01HL053989 · NHLBI · VANDERBILT UNIVERSITY · PI LINTON, MACRAE F · 1995 to 2003
$1.5M
NHLBI NIH HHS HL57986NHLBI NIH HHS HL57989NHLBI NIH HHS HL65405NHLBI NIH HHS HL65709NHLBI NIH HHS R01 HL053989NHLBI NIH HHS R01 HL057986NHLBI NIH HHS R01 HL065405NHLBI NIH HHS R01 HL065709NHLBI NIH HHS R01 HL086988NIDDK NIH HHS P30 DK020593NIDDK NIH HHS P60 DK020593NIDDK NIH HHS P60DK20593
6 · The paper itself

Abstract

objectiveWe used genetically engineered mouse hematopoietic progenitor cells (HPCs) to investigate the therapeutic effects of human apoAI on atherosclerosis in apoE(-/-) mice. METHODS AND

resultsLentiviral constructs expressing either human apoAI (LV-apoAI) or green fluorescent protein (LV-GFP) cDNA under a macrophage specific promoter (CD68) were generated and used for ex vivo transduction of mouse HPCs and macrophages. The transduction efficiency was >25% for HPCs and >70% for macrophages. ApoAI was found in the macrophage culture media, mostly associated with the HDL fraction. Interestingly, a significant increase in mRNA and protein levels for ATP binding cassette A1 (ABCA1) and ABCG1 were found in apoAI-expressing macrophages after acLDL loading. Expression of apoAI significantly increased cholesterol efflux in wild-type and apoE(-/-) macrophages. HPCs transduced with LV-apoAI ex vivo and then transplanted into apoE(-/-) mice caused a 50% reduction in atherosclerotic lesion area compared to GFP controls, without influencing plasma HDL-C levels.

conclusionsLentiviral transduction of apoAI into HPCs reduces atherosclerosis in apoE(-/-) mice. Expression of apoAI in macrophages improves cholesterol trafficking in wild-type apoE-producing macrophages and causes upregulation of ABCA1 and ABCG1. These novel observations set the stage for a cell therapy approach to atherosclerosis regression, exploiting the cooperation between apoE and apoAI to maximize cholesterol exit from the plaque.

Indexed as

AnimalsAortaApolipoprotein A-IAtherosclerosisDisease Models, AnimalFemaleGenetic TherapyHematopoietic Stem Cell TransplantationLentivirusMacrophagesMaleRatsTransduction, GeneticApolipoprotein A-I

Identifiers

PMID18497309
PMCPMC2744493
OpenAlexW2008272749

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.