Evidence map›Paper›PMID 32871430›Full record

ArticleThe Journal of surgical research2021

PERK Inhibition Promotes Post-angioplasty Re-endothelialization via Modulating SMC Phenotype Changes.

Bowen Wang, Mengxue Zhang, Go Urabe, Takuro Shirasu, Lian-Wang Guo, K Craig Kent

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

Article in The Journal of surgical research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 35% 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

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Targeted NADJournal of controlled release : official journal of the Controlled Release Society · 2024
    Article
  6. Article
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  8. Extracellular Vesicles and Ischemic Cardiovascular Diseases.Advances in experimental medicine and biology · 2023
    Article
  9. Biomimetic, ROS-detonable nanoclusters - A multimodal nanoplatform for anti-restenotic therapy.Journal of controlled release : official journal of the Controlled Release Society · 2021
    Article
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

6 authors at 3 institutions in 1 country.

Bowen WangDavis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio; Department of Surgery, College of Medicine, The Ohio State University, Columbus, Ohio; Department of Surgery, School of Medicine, University of Virginia, Charlottesville, Virginia.
Mengxue ZhangDavis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio; Department of Surgery, College of Medicine, The Ohio State University, Columbus, Ohio; Cellular and Molecular Pathology Graduate Program, Department of Pathology, University of Wisconsin-Madison, Madison, Wisconsin.
Go UrabeDavis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio; Department of Surgery, College of Medicine, The Ohio State University, Columbus, Ohio.
Takuro ShirasuDavis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio; Department of Surgery, College of Medicine, The Ohio State University, Columbus, Ohio; Department of Surgery, School of Medicine, University of Virginia, Charlottesville, Virginia; Department of Physiology & Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio.
Lian-Wang GuoDavis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio; Department of Surgery, College of Medicine, The Ohio State University, Columbus, Ohio; Department of Surgery, School of Medicine, University of Virginia, Charlottesville, Virginia; Department of Physiology & Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio. Electronic address: LG8ZR@virginia.edu.
K Craig KentDepartment of Surgery, College of Medicine, The Ohio State University, Columbus, Ohio; Department of Surgery, School of Medicine, University of Virginia, Charlottesville, Virginia. Electronic address: CK8AQ@virginia.edu.
The Ohio State University Wexner Medical Center · USUniversity of Virginia · USUniversity of Wisconsin–Madison · US

Funding

Targeting PERK: An Endothelium-Protective Stent-Free Strategy for Mitigation of Intimal Hyperplasia After Vascular SurgeryR01HL143469 · NHLBI · UNIVERSITY OF VIRGINIA · PI GONG, SHAOQIN -, GUO, LIANWANG · 2018 to 2021
$2.4M
Development of unimolecular nanoparticle-mediated periadventitial drug delivery system for sustained and targeted inhibition of intimal hyperplasia following open vascular reconstructionR01HL129785 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI GONG, SHAOQIN -, GUO, LIANWANG · 2016 to 2019
$2.0M
BET Bromodomain proteins as Novel Epigenetic Targets for prevention of Intimal Hyperplasia after Vascular SurgeryR01HL133665 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI GUO, LIANWANG · 2016 to 2019
$1.6M
NHLBI NIH HHS R01 HL129785NHLBI NIH HHS R01 HL133665NHLBI NIH HHS R01 HL143469
6 · The paper itself

Abstract

backgroundDrug-eluting stents impair post-angioplasty re-endothelialization thus compromising restenosis prevention while heightening thrombotic risks. We recently found that inhibition of protein kinase RNA-like endoplasmic reticulum kinase (PERK) effectively mitigated both restenosis and thrombosis in rodent models. This motivated us to determine how PERK inhibition impacts re-endothelialization.

methodsRe-endothelialization was evaluated in endothelial-denuded rat carotid arteries after balloon angioplasty and periadventitial administration of PERK inhibitor in a hydrogel. To study whether PERK in smooth muscle cells (SMCs) regulates re-endothelialization by paracrinally influencing endothelial cells (ECs), denuded arteries exposing SMCs were lentiviral-infected to silence PERK; in vitro, the extracellular vesicles isolated from the medium of PDGF-activated, PERK-upregulating human primary SMCs were transferred to human primary ECs.

resultsTreatment with PERK inhibitor versus vehicle control accelerated re-endothelialization in denuded arteries. PERK-specific silencing in the denuded arterial wall (mainly SMCs) also enhanced re-endothelialization compared to scrambled shRNA control. In vitro, while medium transfer from PDGF-activated SMCs impaired EC viability and increased the mRNA levels of dysfunctional EC markers, either PERK inhibition or silencing in donor SMCs mitigated these EC changes. Furthermore, CXCL10, a paracrine cytokine detrimental to ECs, was increased by PDGF activation and decreased after PERK inhibition or silencing in SMCs.

conclusionsAttenuating PERK activity pharmacologically or genetically provides an approach to accelerating post-angioplasty re-endothelialization in rats. The mechanism may involve paracrine factors regulated by PERK in SMCs that impact neighboring ECs. This study rationalizes future development of PERK-targeted endothelium-friendly vascular interventions.

Indexed as

Angioplasty, BalloonAnimalsCarotid ArteriesCoronary RestenosisDisease Models, AnimalDrug-Eluting StentseIF-2 KinaseEndothelial CellsEndothelium, VascularHumansMaleMuscle, Smooth, VascularMyocytes, Smooth MuscleParacrine CommunicationProtein Kinase InhibitorsRatseIF-2 KinaseProtein Kinase InhibitorsRNA, Small InterferingAngioplastyEndothelial cellPERKRe-endothelializationSmooth muscle cell

Identifiers

PMID32871430
PMCPMC11034999
OpenAlexW3082668623

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.