Evidence map›Paper›PMID 32087218›Full record

ArticleJournal of molecular and cellular cardiology2020

IRF-1 mediates the suppressive effects of mTOR inhibition on arterial endothelium.

Kai Peng, Xing Fan, Qiannan Li, Yiying Wang, Xiaolin Chen, Pingxi Xiao, Anthony G Passerini, Scott I Simon, ChongXiu Sun

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular and cellular cardiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

8 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. The role of Th9 CD4Journal of clinical laboratory analysis · 2022
    Article
  5. Article
  6. Article
  7. Review
  8. Review
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

9 authors at 2 institutions in 2 countries.

Kai PengKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China; Key laboratory of Human Functional Genomics of Jiang Province, Nanjing, China.
Xing FanKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China; Key laboratory of Human Functional Genomics of Jiang Province, Nanjing, China.
Qiannan LiKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China; Key laboratory of Human Functional Genomics of Jiang Province, Nanjing, China.
Yiying WangKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China; Key laboratory of Human Functional Genomics of Jiang Province, Nanjing, China.
Xiaolin ChenKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China; Key laboratory of Human Functional Genomics of Jiang Province, Nanjing, China.
Pingxi XiaoDepartment of Cardiology, The affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing, China.
Anthony G PasseriniDepartment of Biomedical Engineering, University of California Davis, Davis, CA, United States of America.
Scott I SimonDepartment of Biomedical Engineering, University of California Davis, Davis, CA, United States of America.
ChongXiu SunKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China; Key laboratory of Human Functional Genomics of Jiang Province, Nanjing, China. Electronic address: cxsun@njmu.edu.cn.
Nanjing Medical University · CNUniversity of California, Davis · US

Funding

Outside-in Mechanotransduced Inflammatory TargetsR01AI047294 · NIAID · UNIVERSITY OF CALIFORNIA DAVIS · PI SIMON, SCOTT IRWIN · 1999 to 2021
$7.0M
NIAID NIH HHS R01 AI047294
6 · The paper itself

Abstract

aimsMammalian target of rapamycin (mTOR) inhibitors used in drug-eluting stents (DES) to control restenosis have been found to delay endothelialization and increase incidence of late-stent thrombosis through mechanisms not completely understood. We revealed that mTOR inhibition (mTORi) upregulated the expression of cell growth suppressor IRF-1 in primary human arterial endothelial cells (HAEC). This study aimed to examine how mTOR-regulated IRF-1 expression contributes to the suppressive effect of mTORi on arterial endothelial proliferation. METHODS AND

resultsWestern blotting, quantitative PCR, and a dual-luciferase reporter assay indicated that mTOR inhibitors rapamycin and torin 1 upregulated IRF-1 expression and increased its transcriptional activity. IRF-1 in turn contributed to the suppressive effect of mTORi by mediating HAEC apoptosis and cell cycle arrest in part through upregulation of caspase 1 and downregulation of cyclin D3, as revealed by CCK-8 assay, Annexin V binding assay, measurement of activated caspase 3, BrdU incorporation assay, and matrigel tube formation assay. In a mouse model of femoral artery wire injury, administration of rapamycin inhibited EC recovery, an effect alleviated by EC deficiency of IRF-1. Chromatin immunoprecipitation assay with HAEC and rescue expression of wild type or dominant-negative IRF-1 in EC isolated from Irf1

conclusionsThe study reveals an IRF-1-mediated mechanism that contributes to the suppressive effects of mTORi on HAEC proliferation. Further study may facilitate the development of effective strategies to reduce the side effects of DES used in coronary interventions.

Indexed as

AnimalsApoptosisCell Cycle CheckpointsCell ProliferationCells, CulturedEndothelial CellsEndothelium, VascularFemoral ArteryHumansInterferon Regulatory Factor-1MiceMice, KnockoutNaphthyridinesSignal TransductionSirolimusTOR Serine-Threonine Kinases1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-oneInterferon Regulatory Factor-1IRF1 protein, humanIrf1 protein, mouseMTOR protein, humanmTOR protein, mouseNaphthyridinesSirolimusTOR Serine-Threonine KinasesCell proliferationDrug-eluting stentsEndotheliummTORTranscription factor

Identifiers

PMID32087218
PMCPMC7138750
OpenAlexW3007110402

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.