Evidence map›Paper›PMID 30761006›Full record

ArticleFrontiers in pharmacology2019

CRP-Induced NLRP3 Inflammasome Activation Increases LDL Transcytosis Across Endothelial Cells.

Fang Bian, Xiao-Yan Yang, Gao Xu, Tao Zheng, Si Jin

Open access · goldAbstract read
In one paragraph

Article in Frontiers in pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
2.7field-weighted citation impact, top 9% 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

44 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 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

5 authors at 3 institutions in 1 country.

Fang BianDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xiao-Yan YangDepartment of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Gao XuDepartment of Pharmacy, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Tao ZhengDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Si JinDepartment of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Huazhong University of Science and Technology · CNHubei University of Arts and Science · CNWuhan Union Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The NLRP3 inflammasome, a multiprotein cytosolic complex that activates the IL-1 family of cytokines, plays an important role in atherosclerosis (AS). High-sensitivity c-reactive protein (hs-CRP) is widely recognized as a major cardiovascular risk predictor and recent studies name NLRP3 as a predictor of CRP levels. Mounting evidence has indicated that subendothelial retention of apolipoprotein B100-containing lipoproteins, such as low-density lipoprotein (LDL), is the initial step of atherogenesis, and is usually termed the "response to retention hypothesis." We previously reported that CRP promotes AS by directly increasing LDL transcytosis across endothelial cells (ECs). The present study aims to investigate the effects of CRP on NLRP3 inflammasome activation and the role of the NLRP3 inflammasome in CRP-induced LDL transcytosis. We found that CRP upregulated NF-κB activity, the NF-κB inhibitor (BAY-11-7082) and Fcγ receptors (FcγRs) inhibitor (CD32/64Ab) blocked CRP-induced NF-κB activation. CRP also induced expression of pro-IL-1β and NLRP3, while BAY and CD32/64 Ab suppressed CRP-mediated expression of NLRP3 and pro-IL-1β. Moreover, CRP activated the NLRP3 inflammasome in ECs. NADPH oxidase inhibitor, diphenylene iodonium (DPI) and dithiothreitol (DTT), a broad-spectrum P2 receptor inhibitor, oxidized ATP (oATP), and a broad inhibitor of cysteine proteases, E-64d, inhibited CRP-induced NLRP3 inflammasome activation. Furthermore, NLRP3 siRNA and caspase-1 inhibitor blocked CRP-mediated LDL transcytosis across ECs. In conclusion, NLRP3 inflammasome activation was shown to be involved in CRP-mediated LDL transcytosis across ECs. CRP not only increased the expression of pro-IL-1β and NLRP3 via the FcγRs/NF-κB pathway, but also promoted NLRP3 inflammasome activation and IL-1β maturation by upregulation of reactive oxygen species (ROS) levels, purinergic receptor signaling, and activation of cysteine proteases.

Indexed as

C-reactive proteinendothelial cellslow density lipoproteinNLRP3 inflammasometranscytosis

Identifiers

PMID30761006
PMCPMC6363700
OpenAlexW2911914952

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.