Evidence map›Paper›PMID 39056563›Full record

ArticleCardiovascular research2024

Inhibition of endothelial-to-mesenchymal transition in a large animal preclinical arteriovenous fistula model leads to improved remodelling and reduced stenosis.

Yang Xu, Adam Korayem, Ana S Cruz-Solbes, Nirupama Chandel, Tomoki Sakata, Renata Mazurek, Spyros A Mavropoulos, Taro Kariya, Tadao Aikawa, Kelly P Yamada and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
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

7 citing papers in PubMed.

  1. A Vein Attempt? Experimental Models for Arteriovenous Fistula Research.Cardiovascular engineering and technology · 2026
    Review
  2. Observational
  3. Review
  4. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Yang XuCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.
Adam KorayemDivision of Vascular Surgery, Department of Surgery, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Ana S Cruz-SolbesCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.
Nirupama ChandelCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.
Tomoki SakataCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.
Renata MazurekCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.
Spyros A MavropoulosCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.
Taro KariyaCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.
Tadao AikawaCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.ORCID 0000-0002-1786-0176
Kelly P YamadaCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.
Valentina D'EscamardCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.
Bhargavi V'GangulaCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.
Andrew H BakerCentre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
Lijiang MaCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.
Johan L M BjörkegrenCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.
Valentin FusterCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.
Manfred BoehmLaboratory of Cardiovascular Regenerative Medicine, Translational Vascular Medicine Branch, National Heart Lung and Blood Institute, NIH, Bethesda, MD, USA.ORCID 0000-0002-2251-3638
Kenneth M FishCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.
Rami TadrosDivision of Vascular Surgery, Department of Surgery, Mount Sinai Hospital, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Kiyotake IshikawaCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.
Jason C KovacicCardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1014, New York, NY 10029, USA.ORCID 0000-0003-4555-769X

Funding

Murine models of vascular remodelingZIAHL006078 · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · 2025 to 2025
$1.0M
New York Consortium for Interdisciplinary Training in Kidney, Urological and Hematological Research (NYC Train KUHR)TL1DK136048 · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2025 to 2025
$708k
Haver FoundationKUHR ConsortiumNHLBI NIH HHS R01 HL130423NHLBI NIH HHS R01 HL135093NIDDK NIH HHS TL1 DK136048NIH HHS R01HL130423
6 · The paper itself

Abstract

aimsVein grafts are used for many indications, including bypass graft surgery and arteriovenous fistula (AVF) formation. However, patency following vein grafting or AVF formation is suboptimal for various reasons, including thrombosis, neointimal hyperplasia, and adverse remodelling. Recently, endothelial-to-mesenchymal transition (EndMT) was found to contribute to neointimal hyperplasia in mouse vein grafts. We aimed to evaluate the clinical potential of inhibiting EndMT and developed the first dedicated preclinical model to study the efficacy of local EndMT inhibition immediately prior to AVF creation. METHODS AND

resultsWe first undertook pilot studies to optimize the creation of a femoral AVF in pigs and verify that EndMT contributes to neointimal formation. We then developed a method to achieve local in vivo SMAD3 knockdown by dwelling a lentiviral construct containing SMAD3 shRNA in the femoral vein prior to AVF creation. Next, in Phase 1, six pigs were randomized to SMAD3 knockdown or control lentivirus to evaluate the effectiveness of SMAD3 knockdown and EndMT inhibition 8 days after AVF creation. In Phase 2, 16 pigs were randomized to SMAD3 knockdown or control lentivirus and were evaluated to assess longer-term effects on AVF diameter, patency, and related measures at 30 days after AVF creation. In Phase 1, compared with controls, SMAD3 knockdown achieved a 75% reduction in the proportion of CD31+ endothelial cells co-expressing SMAD3 (P < 0.001) and also a significant reduction in the extent of EndMT (P < 0.05). In Phase 2, compared with controls, SMAD3 knockdown was associated with an increase in the minimum diameter of the venous limb of the AVF (1.56 ± 1.66 vs. 4.26 ± 1.71 mm, P < 0.01) and a reduced degree of stenosis (P < 0.01). Consistent with this, neointimal thickness was reduced in the SMAD3 knockdown group (0.88 ± 0.51 vs. 0.45 ± 0.19 mm, P < 0.05). Furthermore, endothelial integrity (the proportion of luminal cells expressing endothelial markers) was improved in the SMAD3 knockdown group (P < 0.05).

conclusionEndMT inhibition in a preclinical AVF model by local SMAD3 knockdown using gene therapy led to reduced neointimal hyperplasia, increased endothelialization, and a reduction in the degree of AVF stenosis. This provides important proof of concept to pursue this approach as a clinical strategy to improve the patency of AVFs and other vein grafts.

Indexed as

Arteriovenous Shunt, SurgicalDisease Models, AnimalNeointimaSmad3 ProteinVascular PatencyVascular RemodelingAnimalsEndothelial CellsEpithelial-Mesenchymal TransitionFemoral ArteryFemoral VeinGraft Occlusion, VascularMalePilot ProjectsRNA InterferenceSignal TransductionSmad3 ProteinArteriovenous fistulaEndothelial-to-mesenchymal transitionNeointimaStenosisVein graft

Identifiers

PMID39056563
PMCPMC11587554

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.