Evidence map›Paper›PMID 29072256›Full record

ArticleActa pharmacologica Sinica2018

Rapamycin inhibits ox-LDL-induced inflammation in human endothelial cells in vitro by inhibiting the mTORC2/PKC/c-Fos pathway.

Juan-Juan Sun, Xiao-Wei Yin, Hui-Hui Liu, Wen-Xiu Du, Lu-Yao Shi, Ya-Bo Huang, Fen Wang, Chun-Feng Liu, Yong-Jun Cao, Yan-Lin Zhang

Open access · bronzeAbstract read
In one paragraph

Article in Acta pharmacologica Sinica, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

21 citing papers in PubMed, 37 citations in OpenAlex.

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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

10 authors at 2 institutions in 2 countries.

Juan-Juan SunDepartment of Neurology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Xiao-Wei YinDepartment of Neurology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Hui-Hui LiuDepartment of Neurology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Wen-Xiu DuDepartment of Neurology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Lu-Yao ShiDepartment of Neurology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Ya-Bo HuangDepartment of Neurosurgery, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Fen WangJiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou 215123, China.
Chun-Feng LiuDepartment of Neurology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Yong-Jun CaoDepartment of Neurology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Yan-Lin ZhangDepartment of Neurology, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
Second Affiliated Hospital of Soochow University · CNSoochow University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rapamycin and its derivative possess anti-atherosclerosis activity, but its effects on adhesion molecule expression and macrophage adhesion to endothelial cells during atherosclerosis remain unclear. In this study we explored the effects of rapamycin on ox-LDL-induced adhesion molecule expression and macrophage adhesion to endothelial cells in vitro and the underlying mechanisms. Ox-LDL (6-48 μg/mL) dose-dependently increased the protein levels of two adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and E-selectin, in human umbilical vein endothelial cells (HUVECs), whereas pretreatment with rapamycin (1-10 μmol/L) dose-dependently inhibited ox-LDL-induced increase in the adhesion molecule expression and macrophage adhesion to endothelial cells. Knockdown of mTOR or rictor, rather than raptor, mimicked the effects of rapamycin. Ox-LDL (100 μg/mL) time-dependently increased PKC phosphorylation in HUVECs, which was abolished by rapamycin or rictor siRNA. Pretreatment with PKC inhibitor staurosporine significantly reduced ox-LDL-stimulated adhesion molecule expression and macrophage adhesion to endothelial cells, whereas pretreatment with PKC activator PMA/TPA attenuated the inhibitory effect of rapamycin on adhesion molecule expression. Ox-LDL (100 μg/mL) time-dependently increased c-Fos levels in HUVECs, and pretreatment with rapamycin or rictor siRNA significantly decreased expression of c-Fos. Knockdown of c-Fos antagonized ox-LDL-induced adhesion molecule expression and macrophage adhesion to endothelial cells. Our results demonstrate that rapamycin reduces ox-LDL-stimulated adhesion molecule expression and macrophage adhesion to endothelial cells by inhibiting mTORC2, but not mTORC1, and mTORC2 acts through the PKC/c-Fos signaling pathway.

Indexed as

Cell AdhesionCells, CulturedDose-Response Relationship, DrugE-SelectinGene Knockdown TechniquesGenes, fosHumansHuman Umbilical Vein Endothelial CellsInflammationIntercellular Adhesion Molecule-1Lipoproteins, LDLMechanistic Target of Rapamycin Complex 2Protein Kinase CRapamycin-Insensitive Companion of mTOR ProteinRegulatory-Associated Protein of mTORRNA, Small Interfering4-O-methyl-12-O-tetradecanoylphorbol 13-acetateE-SelectinIntercellular Adhesion Molecule-1Lipoproteins, LDLMechanistic Target of Rapamycin Complex 2oxidized low density lipoproteinProtein Kinase CRapamycin-Insensitive Companion of mTOR ProteinRegulatory-Associated Protein of mTORRICTOR protein, humanRNA, Small InterferingRPTOR protein, humanSirolimusStaurosporineTetradecanoylphorbol Acetate

Identifiers

PMID29072256
PMCPMC5843827
OpenAlexW2765739569

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.