Evidence map›Paper›PMID 38077163›Full record

ArticleJVS-vascular science2023

Ceramides in peripheral arterial plaque lead to endothelial cell dysfunction.

Rodrigo Meade, Yang Chao, Nikolai Harroun, Chenglong Li, Shahab Hafezi, Fong-Fu Hsu, Clay F Semenkovich, Mohamed A Zayed

Open access · goldAbstract read
In one paragraph

Article in JVS-vascular science, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

10 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Article
  3. Observational
  4. The Role of Ceramides in Metabolic and Cardiovascular Diseases.Journal of cardiovascular development and disease · 2026
    Review
  5. Review
  6. Endothelial CEPT1 Promotes Angiogenesis Through PPARα and VEGF-A Signaling.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Article
  7. Review
  8. Ceramide as a Biomarker for HFpEF in Women: Menopause, Aging, and Pregnancy.International journal of molecular sciences · 2025
    Review
  9. Article
  10. 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

8 authors at 1 institution in 1 country.

Rodrigo MeadeSection of Vascular Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO.
Yang ChaoSection of Vascular Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO.
Nikolai HarrounSection of Vascular Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO.
Chenglong LiSection of Vascular Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO.
Shahab HafeziSection of Vascular Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO.
Fong-Fu HsuDivision of Endocrinology, Lipid, and Metabolism, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
Clay F SemenkovichDivision of Endocrinology, Lipid, and Metabolism, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
Mohamed A ZayedSection of Vascular Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO.
Washington University in St. Louis · US

Funding

Washington University Nutrition Obesity Research CenterP30DK056341 · NIDDK · WASHINGTON UNIVERSITY · PI Brian N Finck · 1999 to 2026
$30.2M
WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Irfan J Lodhi · 2013 to 2026
$27.1M
TRANSGENICS COREP60DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI SCHAFFER, JEAN E. · 1986 to 2012
$25.2M
TrainingP41GM103422 · NIGMS · WASHINGTON UNIVERSITY · PI YARASHESKI, KEVIN E · 2012 to 2019
$12.0M
PET Detection of CCR2 in Human AtherosclerosisR01HL150891 · NHLBI · WASHINGTON UNIVERSITY · PI GROPLER, ROBERT J., WOODARD, PAMELA K · 2020 to 2024
$3.7M
Regulation of Endothelial Lipid Metabolism in the Setting of Diabetes and Critical Limb Ischemia to Prevent Surgical ComplicationsR01HL153262 · NHLBI · WASHINGTON UNIVERSITY · PI ZAYED, MOHAMED A. · 2021 to 2024
$2.1M
MODULATING PHYSIOLOGIC EFFECTS OF PHOSPHOLIPID METABOLISM IN OBESITY AND DIABETESR01DK101392 · NIDDK · WASHINGTON UNIVERSITY · PI SEMENKOVICH, CLAY F. · 2015 to 2019
$2.0M
Lipidation and Vascular DiseaseR01HL157154 · NHLBI · WASHINGTON UNIVERSITY · PI SEMENKOVICH, CLAY F. · 2021 to 2024
$1.6M
THE ROLE OF PHOSPHOLIPOGENESIS IN DIABETIC PERIPHERAL ARTERIAL DISEASEK08HL132060 · NHLBI · WASHINGTON UNIVERSITY · PI ZAYED, MOHAMED A. · 2017 to 2021
$466k
NHLBI NIH HHS K08 HL132060NHLBI NIH HHS R01 HL150891NHLBI NIH HHS R01 HL153262NHLBI NIH HHS R01 HL157154NIDDK NIH HHS P30 DK020579NIDDK NIH HHS P30 DK056341NIDDK NIH HHS P60 DK020579NIDDK NIH HHS R01 DK101392NIGMS NIH HHS P41 GM103422
6 · The paper itself

Abstract

Background: Peripheral arterial atheroprogression is increasingly prevalent, and is a risk factor for major limb amputations in individuals with risk factors such as diabetes. We previously demonstrated that bioactive lipids are significantly altered in arterial tissue of individuals with diabetes and advanced peripheral arterial disease. Methods: Here we evaluated whether sphingolipid ceramide 18:1/16:0 (C16) is a cellular regulator in endothelial cells and peripheral tibial arterial tissue in individuals with diabetes. Results: We observed that C16 is the single most elevated ceramide in peripheral arterial tissue from below the knee in individuals with diabetes (11% increase, Conclusions: Our findings suggest that C16 is a tissue biomarker for peripheral arterial disease severity in the setting of diabetes, and can impact endothelial cell viability and function. Clinical relevance: Peripheral arterial disease and its end-stage manifestation known as chronic limb-threatening ischemia (CLTI) represent ongoing prevalent and intricate medical challenges. Individuals with diabetes have a heightened risk of developing CLTI and experiencing its complications, including wounds, ulcers, and major amputations. In the present study, we conducted a comprehensive examination of the molecular lipid composition within arterial segments from individuals with CLTI, and with and without diabetes. Our investigations unveiled a striking revelation: the sphingolipid ceramide 18:1/16:0 emerged as the predominant ceramide species that was significantly elevated in the peripheral arterial intima below the knee in patients with diabetes. Moreover, this heightened ceramide presence is associated with a marked impairment of endothelial cell function and viability. Additionally, our study revealed a concurrent elevation in the expression of sphingomyelin phosphodiesterases, enzymes responsible for catalyzing ceramide synthesis from sphingomyelins, within maximally diseased arterial segments. These findings underscore the pivotal role of ceramides and their biosynthesis enzymes in the context of CLTI, offering new insights into potential therapeutic avenues for managing this challenging disease process.

Indexed as

CeramideDiabetesEndothelial dysfunctionPeripheral arterial diseaseSphingolipidSphingomyelinase

Identifiers

PMID38077163
PMCPMC10704331
OpenAlexW4388599564

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.