Evidence map›Paper›PMID 10377075›Full record

ArticleCirculation1999

PPARalpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells.

N Marx, G K Sukhova, T Collins, P Libby, J Plutzky

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
147citing papers in PubMed, 1 pooled it
12.7field-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

147 citing papers in PubMed, 1 synthesis or guideline pooled it, 595 citations in OpenAlex.

  1. Pooled it
  2. Diabetes · 2020
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  7. Bibliometric analysis of residual cardiovascular risk: trends and frontiers.Journal of health, population, and nutrition · 2023
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  19. Pathophysiology of Atherosclerosis.International journal of molecular sciences · 2022
    Review
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87 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

5 authors at 1 institution in 1 country.

N MarxVascular Medicine and Atherosclerosis Unit, Cardiovascular Division and the Vascular Research Division, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
G K Sukhova
T Collins
P Libby
J Plutzky
Brigham and Women's Hospital · US

Funding

Tissue AnalysesP01HL048743 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI MICHEL, THOMAS · 1992 to 2014
$26.3M
Lipolytic Mechanisms of PPAR ActivationR01HL071745 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI PLUTZKY, JORGE · 2004 to 2007
$1.6M
NHLBI NIH HHS HL-03107NHLBI NIH HHS HL-48743NHLBI NIH HHS P01 HL048743NHLBI NIH HHS R01 HL071745
6 · The paper itself

Abstract

backgroundAdhesion molecule expression on the endothelial cell (EC) surface is critical for leukocyte recruitment to atherosclerotic lesions. Better understanding of transcriptional regulation of adhesion molecules in ECs may provide important insight into plaque formation. Peroxisome proliferator-activated receptor-alpha (PPARalpha), a member of the nuclear receptor family, regulates gene expression in response to certain fatty acids and fibric acid derivatives. The present study investigated PPARalpha expression in human ECs and their regulation of vascular cell adhesion molecule-1 (VCAM-1). METHODS AND

resultsImmunohistochemistry revealed that human carotid artery ECs express PPARalpha. Pretreatment of cultured human ECs with the PPARalpha activators fenofibrate or WY14643 inhibited TNF-alpha-induced VCAM-1 in a time- and concentration-dependent manner, an effect not seen with PPARgamma activators. Both PPARalpha activators decreased cytokine-induced VCAM-1 mRNA expression without altering its mRNA half-life. Transient transfection of deletional VCAM-1 promoter constructs and electrophoretic mobility shift assays suggest that fenofibrate inhibits VCAM-1 transcription in part by inhibiting NF-kappaB. Finally, PPARalpha activators significantly reduced adhesion of U937 cells to cultured human ECs.

conclusionsHuman ECs express PPARalpha, a potentially important regulator of atherogenesis through its transcriptional control of VCAM-1 gene expression. Such findings also have implications regarding the clinical use of lipid-lowering agents, like fibric acids, which can activate PPARalpha.

Indexed as

Anticholesteremic AgentsArteriosclerosisCarotid ArteriesCell AdhesionDose-Response Relationship, DrugEndothelium, VascularFenofibrateGene ExpressionHumansHypolipidemic AgentsMonocytesNF-kappa BPromoter Regions, GeneticPyrimidinesReceptors, Cytoplasmic and NuclearRNA, MessengerAnticholesteremic AgentsFenofibrateHypolipidemic AgentsNF-kappa Bpirinixic acidPyrimidinesReceptors, Cytoplasmic and NuclearRNA, MessengerTranscription FactorsTumor Necrosis Factor-alphaVascular Cell Adhesion Molecule-1

Identifiers

PMID10377075
PMCPMC4231776
OpenAlexW2050904588

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.