Evidence map›Paper›PMID 34912867›Full record

ArticleFrontiers in cardiovascular medicine2021

Novel Knowledge-Based Transcriptomic Profiling of Lipid Lysophosphatidylinositol-Induced Endothelial Cell Activation.

Keman Xu, Ying Shao, Fatma Saaoud, Aria Gillespie, Charles Drummer, Lu Liu, Yifan Lu, Yu Sun, Hang Xi, Çagla Tükel and 7 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in cardiovascular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.5field-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

20 citing papers in PubMed, 22 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

17 authors at 3 institutions in 1 country.

Keman XuCenters of Cardiovascular Research, Inflammation and Lung Research, Philadelphia, PA, United States.
Ying ShaoCenters of Cardiovascular Research, Inflammation and Lung Research, Philadelphia, PA, United States.
Fatma SaaoudCenters of Cardiovascular Research, Inflammation and Lung Research, Philadelphia, PA, United States.
Aria GillespieNeural Sciences, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United States.
Charles DrummerCenters of Cardiovascular Research, Inflammation and Lung Research, Philadelphia, PA, United States.
Lu LiuDepartments of Cardiovascular Sciences, Metabolic Disease Research, Thrombosis Research, Philadelphia, PA, United States.
Yifan LuCenters of Cardiovascular Research, Inflammation and Lung Research, Philadelphia, PA, United States.
Yu SunCenters of Cardiovascular Research, Inflammation and Lung Research, Philadelphia, PA, United States.
Hang XiDepartments of Cardiovascular Sciences, Metabolic Disease Research, Thrombosis Research, Philadelphia, PA, United States.
Çagla TükelCenter for Microbiology & Immunology, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United States.
Domenico PraticoAlzheimer's Center, Temple University Lewis Katz School of Medicine, Philadelphia, PA, United States.
Xuebin QinNational Primate Research Center, Tulane University, Covington, LA, United States.
Jianxin SunDepartment of Medicine, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, United States.
Eric T ChoiSurgery (Division of Vascular and Endovascular Surgery), Temple University Lewis Katz School of Medicine, Philadelphia, PA, United States.
Xiaohua JiangCenters of Cardiovascular Research, Inflammation and Lung Research, Philadelphia, PA, United States.
Hong WangDepartments of Cardiovascular Sciences, Metabolic Disease Research, Thrombosis Research, Philadelphia, PA, United States.
Xiaofeng YangCenters of Cardiovascular Research, Inflammation and Lung Research, Philadelphia, PA, United States.
Temple University · USThomas Jefferson University · USTulane University · US

Funding

Tulane NPRC SPF Sheltered Outdoor Enclosure ExpansionP51OD011104 · OD · TULANE UNIVERSITY OF LOUISIANA · PI L Lee HAMM · 2012 to 2026
$142.4M
NIH HHS P51 OD011104
6 · The paper itself

Abstract

To determine whether pro-inflammatory lipid lysophosphatidylinositols (LPIs) upregulate the expressions of membrane proteins for adhesion/signaling and secretory proteins in human aortic endothelial cell (HAEC) activation, we developed an EC biology knowledge-based transcriptomic formula to profile RNA-Seq data panoramically. We made the following primary findings: first, G protein-coupled receptor 55 (GPR55), the LPI receptor, is expressed in the endothelium of both human and mouse aortas, and is significantly upregulated in hyperlipidemia; second, LPIs upregulate 43 clusters of differentiation (CD) in HAECs, promoting EC activation, innate immune trans-differentiation, and immune/inflammatory responses; 72.1% of LPI-upregulated CDs are not induced in influenza virus-, MERS-CoV virus- and herpes virus-infected human endothelial cells, which hinted the specificity of LPIs in HAEC activation; third, LPIs upregulate six types of 640 secretomic genes (SGs), namely, 216 canonical SGs, 60 caspase-1-gasdermin D (GSDMD) SGs, 117 caspase-4/11-GSDMD SGs, 40 exosome SGs, 179 Human Protein Atlas (HPA)-cytokines, and 28 HPA-chemokines, which make HAECs a large secretory organ for inflammation/immune responses and other functions; fourth, LPIs activate transcriptomic remodeling by upregulating 172 transcription factors (TFs), namely, pro-inflammatory factors NR4A3, FOS, KLF3, and HIF1A; fifth, LPIs upregulate 152 nuclear DNA-encoded mitochondrial (mitoCarta) genes, which alter mitochondrial mechanisms and functions, such as mitochondrial organization, respiration, translation, and transport; sixth, LPIs activate reactive oxygen species (ROS) mechanism by upregulating 18 ROS regulators; finally, utilizing the Cytoscape software, we found that three mechanisms, namely, LPI-upregulated TFs, mitoCarta genes, and ROS regulators, are integrated to promote HAEC activation. Our results provide novel insights into aortic EC activation, formulate an EC biology knowledge-based transcriptomic profile strategy, and identify new targets for the development of therapeutics for cardiovascular diseases, inflammatory conditions, immune diseases, organ transplantation, aging, and cancers.

Indexed as

aortic endothelial cellinflammationRNA-Seq analysissecretomestranscriptomic analysis

Identifiers

PMID34912867
PMCPMC8668339
OpenAlexW3216761115

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.