Evidence map›Paper›PMID 37467597›Full record

ArticleBiomaterials2023

Neointima abating and endothelium preserving - An adventitia-localized nanoformulation to inhibit the epigenetic writer DOT1L.

Takuro Shirasu, Nisakorn Yodsanit, Jing Li, Yitao Huang, Xiujie Xie, Runze Tang, Qingwei Wang, Mengxue Zhang, Go Urabe, Amy Webb and 7 more

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

Article in Biomaterials, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. 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

17 authors at 3 institutions in 1 country.

Takuro ShirasuDivision of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
Nisakorn YodsanitDepartment of Biomedical Engineering and Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Jing LiDivision of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
Yitao HuangDivision of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA; The Biomedical Sciences Graduate Program (BIMS), School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
Xiujie XieDivision of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
Runze TangDivision of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
Qingwei WangDivision of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
Mengxue ZhangDivision of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
Go UrabeDivision of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
Amy WebbDepartment of Biomedical Informatics, College of Medicine, The Ohio State University, Columbus, OH, USA.
Yuyuan WangDepartment of Biomedical Engineering and Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Xiuxiu WangDepartment of Biomedical Engineering and Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Ruosen XieDepartment of Biomedical Engineering and Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53715, USA.
Bowen WangDivision of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
K Craig KentDivision of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA. Electronic address: ck8aq@uvahealth.org.
Shaoqin GongDepartment of Biomedical Engineering and Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, 53715, USA; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, 53715, USA. Electronic address: shaoqingong@wisc.edu.
Lian-Wang GuoDivision of Surgical Sciences, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, VA, 22908, USA; Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, 22908, USA; Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, 22908, USA. Electronic address: lg8zr@virginia.edu.
University of Virginia · USUniversity of Wisconsin–Madison · USThe Ohio State University · 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
The Role of Amino Acid Starvation Response Kinase GCN2 in Abdominal Aortic AneurysmR01HL162895 · NHLBI · UNIVERSITY OF VIRGINIA · PI Bowen Wang · 2022 to 2026
$2.0M
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 HL143469NHLBI NIH HHS R01 HL162895
6 · The paper itself

Abstract

Open vascular reconstructions such as bypass are common treatments for cardiovascular disease. Unfortunately, neointimal hyperplasia (IH) follows, leading to treatment failure for which there is no approved therapy. Here we combined the strengths of tailoring nanoplatforms for open vascular reconstructions and targeting new epigenetic mechanisms. We produced adhesive nanoparticles (ahNP) that could be pen-brushed and immobilized on the adventitia to sustainably release pinometostat, an inhibitor drug selective to the epigenetic writer DOT1L that catalyzes histone-3 lysine-79 dimethylation (H3K79me2). This treatment not only reduced IH by 76.8% in injured arteries mimicking open reconstructions in obese Zucker rats with human-like diseases but also avoided the shortcoming of endothelial impairment in IH management. In mechanistic studies, chromatin immunoprecipitation (ChIP) sequencing revealed co-enrichment of the histone mark H3K27ac(acetyl) and its reader BRD4 at the gene of aurora kinase B (AURKB), where H3K79me2 was also enriched as indicated by ChIP-qPCR. Accordingly, DOT1L co-immunoprecipitated with H3K27ac. Furthermore, the known IH driver BRD4 governed the expression of DOT1L which controlled AURKB's protein level, revealing a BRD4- > DOT1L- > AURKB axis. Consistently, AURKB-selective inhibition reduced IH. Thus, this study presents a prototype nanoformulation suited for open vascular reconstructions, and the new insights into chromatin modulators may aid future translational advances.

Indexed as

AdventitiaNuclear ProteinsAnimalsBromodomain Containing ProteinsCell Cycle ProteinsEndotheliumEpigenesis, GeneticHistone-Lysine N-MethyltransferaseHumansNeointimaRatsRats, ZuckerTranscription FactorsBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsDOT1L protein, humanHistone-Lysine N-MethyltransferaseNuclear ProteinsTranscription FactorsAdhesive nanoparticlesAdventitia-localized nanoformulationsDOT1L inhibitorsEpigenetic targetingNeointima-abating and endothelium-preservingOpen vascular reconstructions

Identifiers

PMID37467597
PMCPMC10530408
OpenAlexW4384156333

What Socratic 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 Socratic graph.