Evidence map›Paper›PMID 23103162›Full record

ArticleCell reports2012

Cardiovascular protection by ApoE and ApoE-HDL linked to suppression of ECM gene expression and arterial stiffening.

Devashish Kothapalli, Shu-Lin Liu, Yong Ho Bae, James Monslow, Tina Xu, Elizabeth A Hawthorne, Fitzroy J Byfield, Paola Castagnino, Shilpa Rao, Daniel J Rader and 5 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed
4.8field-weighted citation impact, top 4% 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

113 citing papers in PubMed, 190 citations in OpenAlex.

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  8. TRPV4-Mediated Mechanosensing Regulates the Endothelial-to-Mesenchymal Transition: Implications for Atherosclerosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
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  15. Transcriptomic and Multi-scale Network Analyses Reveal Key Drivers of Cardiovascular Disease.IEEE transactions on molecular, biological, and multi-scale communications · 2025
    Article
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53 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

15 authors at 4 institutions in 1 country.

Devashish KothapalliInstitute for Translational Medicine and Therapeutics, Departments of Pharmacology, Medicine, and Physiology, and the Molecular Profiling Facility, University of Pennsylvania, Philadelphia, PA 19104, USA.
Shu-Lin Liu
Yong Ho Bae
James Monslow
Tina Xu
Elizabeth A Hawthorne
Fitzroy J Byfield
Paola Castagnino
Shilpa Rao
Daniel J Rader
Ellen Puré
Michael C Phillips
Sissel Lund-Katz
Paul A Janmey
Richard K Assoian
University of Pennsylvania · USTranslational Therapeutics (United States) · USChildren's Hospital of Philadelphia · USThe Wistar Institute · US

Funding

STUDIES OF PLATELET ADHERENCE TO OSTEOPONTINP01HL062250 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 1999 to 2013
$28.4M
TISSUE CULTURE CORE LABORATORYP01HL022633 · NHLBI · MCP HAHNEMANN UNIVERSITY · PI LUND-KATZ, SISSEL · 1985 to 2013
$26.1M
STRUCTURAL BASIS OF THE INTERACTIONS OF APOLIPOPROTEIN ER01HL056083 · NHLBI · MCP HAHNEMANN UNIVERSITY · PI LUND-KATZ, SISSEL · 1997 to 2013
$5.0M
Regulation of smooth muscle cell function by CD44 in cardiovascular diseaseR01HL093283 · NHLBI · WISTAR INSTITUTE · PI PURE', ELLEN · 2009 to 2012
$1.7M
NHLBI NIH HHS HL093283NHLBI NIH HHS HL22633NHLBI NIH HHS HL56083NHLBI NIH HHS HL66250NHLBI NIH HHS P01 HL022633NHLBI NIH HHS P01 HL062250NHLBI NIH HHS R01 HL056083NHLBI NIH HHS R01 HL093283
6 · The paper itself

Abstract

Arterial stiffening is a risk factor for cardiovascular disease, but how arteries stay supple is unknown. Here, we show that apolipoprotein E (apoE) and apoE-containing high-density lipoprotein (apoE-HDL) maintain arterial elasticity by suppressing the expression of extracellular matrix genes. ApoE interrupts a mechanically driven feed-forward loop that increases the expression of collagen-I, fibronectin, and lysyl oxidase in response to substratum stiffening. These effects are independent of the apoE lipid-binding domain and transduced by Cox2 and miR-145. Arterial stiffness is increased in apoE null mice. This stiffening can be reduced by administration of the lysyl oxidase inhibitor BAPN, and BAPN treatment attenuates atherosclerosis despite highly elevated cholesterol. Macrophage abundance in lesions is reduced by BAPN in vivo, and monocyte/macrophage adhesion is reduced by substratum softening in vitro. We conclude that apoE and apoE-containing HDL promote healthy arterial biomechanics and that this confers protection from cardiovascular disease independent of the established apoE-HDL effect on cholesterol.

Indexed as

AminopropionitrileAnimalsAortaApolipoprotein E3Apolipoproteins EAtherosclerosisCells, CulturedCholesterol, HDLCollagen Type ICyclooxygenase 2Extracellular MatrixExtracellular Matrix ProteinsFibronectinsGene ExpressionHumansMacrophagesAminopropionitrileApolipoprotein E3Apolipoproteins ECholesterol, HDLCollagen Type ICyclooxygenase 2Extracellular Matrix ProteinsFibronectinsLox protein, mouseMicroRNAsMIRN145a microRNA, mouseProtein-Lysine 6-Oxidase

Identifiers

PMID23103162
PMCPMC3535179
OpenAlexW2126423643

What OpenQuestion holds

Textmetadata
LicenceTDM
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.