Evidence map›Paper›PMID 37327791›Full record

ArticleCell metabolism2023

Acetate controls endothelial-to-mesenchymal transition.

Xiaolong Zhu, Yunyun Wang, Ioana Soaita, Heon-Woo Lee, Hosung Bae, Nabil Boutagy, Anna Bostwick, Rong-Mo Zhang, Caitlyn Bowman, Yanying Xu and 10 more

Open access · greenAbstract read
In one paragraph

Article in Cell metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
25.6field-weighted citation impact, top 1% 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

70 citing papers in PubMed, 103 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. USP5 Stabilizes TGFBR1 to Drive Vascular Smooth Muscle Cell Senescence and Atherosclerosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  8. Review
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  11. Article
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  19. Single-Cell Metabolic Imaging Reveals Glycogen-Driven Adaptations in Endothelial Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  20. Article

10 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 7 institutions in 3 countries.

Xiaolong ZhuYale Cardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
Yunyun WangMOE Laboratory of Biosystems Homeostasis & Protection of College of Life Sciences, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province of Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
Ioana SoaitaDepartment of Medicine, Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Heon-Woo LeeYale Cardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
Hosung BaeDepartment of Biological Chemistry, University of California Irvine, Irvine, CA, USA.
Nabil BoutagyVascular Biology and Therapeutics Program and Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.
Anna BostwickCenter for Metabolic Disease Research, Department of Cardiovascular Sciences, Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA.
Rong-Mo ZhangYale Cardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
Caitlyn BowmanDepartment of Medicine, Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Yanying XuDepartment of Geriatric Medicine, Coronary Circulation Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Sophie TrefelyEpigenetics and Signaling Program, Babraham Institute, Cambridge, UK.
Yu ChenMOE Laboratory of Biosystems Homeostasis & Protection of College of Life Sciences, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province of Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
Lingfeng QinVascular Biology and Therapeutics Program and Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.
William SessaVascular Biology and Therapeutics Program and Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.
George TellidesVascular Biology and Therapeutics Program and Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.
Cholsoon JangDepartment of Biological Chemistry, University of California Irvine, Irvine, CA, USA.
Nathaniel W SnyderCenter for Metabolic Disease Research, Department of Cardiovascular Sciences, Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA.
Luyang YuMOE Laboratory of Biosystems Homeostasis & Protection of College of Life Sciences, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province of Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address: luyangyu@zju.edu.cn.
Zoltan AranyDepartment of Medicine, Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: zarany@pennmedicine.upenn.edu.
Michael SimonsYale Cardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA. Electronic address: michael.simons@yale.edu.
Yale University · USSir Run Run Shaw Hospital · CNUniversity of Pennsylvania · USTemple University · USUniversity of California, Irvine · USBabraham Institute · GBCentral South University · CN

Funding

Yale Liver CenterP30DK034989 · NIDDK · YALE UNIVERSITY · PI YASUKO IWAKIRI · 1986 to 2026
$31.1M
Surgery / Physiology CoreP01HL107205 · NHLBI · YALE UNIVERSITY · PI SIMONS, MICHAEL · 2012 to 2022
$18.8M
TRAINING PROGRAM IN CELL AND MOLECULAR BIOLOGYT32GM007229 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BARTOLOMEI, MARISA S. · 1985 to 2023
$14.0M
Endothelial-to-mesenchyma transition and atherosclerosisR01HL135582 · NHLBI · YALE UNIVERSITY · PI SCHWARTZ, MARTIN A, SIMONS, MICHAEL · 2017 to 2024
$6.6M
Acetate and Endothelial PathobiologyR01HL167014 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Zoltan P Arany, Michael Simons · 2023 to 2026
$2.8M
Comprehensive quantification of fuel use in cold-induced thermogenesis in vivoR01DK135958 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Zoltan P Arany · 2023 to 2026
$2.3M
Elucidating dietary fructose and alcohol interactions during liver cancer developmentR01AA029124 · NIAAA · UNIVERSITY OF CALIFORNIA-IRVINE · PI JANG, CHOLSOON · 2021 to 2025
$2.0M
Endothelial lipid droplet turnover and regulation of metabolic functionK01DK124441 · NIDDK · YALE UNIVERSITY · PI BOUTAGY, NABIL · 2020 to 2022
$562k
Elucidating the Role of Endothelial NAD Metabolism in AtherosclerosisF31HL158152 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI SOAITA, IOANA · 2021 to 2023
$106k
Biotechnology and Biological Sciences Research Council BB/P013406/1NHLBI NIH HHS F31 HL158152NHLBI NIH HHS P01 HL107205NHLBI NIH HHS R01 HL135582NHLBI NIH HHS R01 HL167014NIAAA NIH HHS R01 AA029124NIDDK NIH HHS K01 DK124441NIDDK NIH HHS P30 DK034989NIDDK NIH HHS R01 DK135958NIGMS NIH HHS T32 GM007229
6 · The paper itself

Abstract

Endothelial-to-mesenchymal transition (EndMT), a process initiated by activation of endothelial TGF-β signaling, underlies numerous chronic vascular diseases and fibrotic states. Once induced, EndMT leads to a further increase in TGF-β signaling, thus establishing a positive-feedback loop with EndMT leading to more EndMT. Although EndMT is understood at the cellular level, the molecular basis of TGF-β-driven EndMT induction and persistence remains largely unknown. Here, we show that metabolic modulation of the endothelium, triggered by atypical production of acetate from glucose, underlies TGF-β-driven EndMT. Induction of EndMT suppresses the expression of the enzyme PDK4, which leads to an increase in ACSS2-dependent Ac-CoA synthesis from pyruvate-derived acetate. This increased Ac-CoA production results in acetylation of the TGF-β receptor ALK5 and SMADs 2 and 4 leading to activation and long-term stabilization of TGF-β signaling. Our results establish the metabolic basis of EndMT persistence and unveil novel targets, such as ACSS2, for the potential treatment of chronic vascular diseases.

Indexed as

Endothelial CellsVascular DiseasesEndotheliumHumansSignal TransductionTransforming Growth Factor betaTransforming Growth Factor betaacetateacetyl-CoAACSS2ALK5atherosclerosisendfothelial cellsendothelial-to-mesenchymal transitionPDK4transforming growth factor beta signaling

Identifiers

PMID37327791
PMCPMC10529701
OpenAlexW4380757896

What OpenQuestion holds

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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 OpenQuestion graph.