Evidence map›Paper›PMID 37381983›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2023

Spatially Resolved Metabolites in Stable and Unstable Human Atherosclerotic Plaques Identified by Mass Spectrometry Imaging.

Erin H Seeley, Zhipeng Liu, Shuai Yuan, Chad Stroope, Elizabeth Cockerham, Nabil A Rashdan, Luisa F Delgadillo, Alexandra C Finney, Dhananjay Kumar, Sandeep Das and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

32 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
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  7. More Than a Cleanup Crew: The Expanding Biology of Efferocytosis.Arteriosclerosis, thrombosis, and vascular biology · 2026
    Review
  8. Article
  9. Article
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  12. Article
  13. Article
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  15. Anti-Atherogenic Mechanisms and Therapies.Current atherosclerosis reports · 2025
    Review
  16. Article
  17. Article
  18. Review
  19. Dissecting inflammation in the immunemetabolomic era.Cellular and molecular life sciences : CMLS · 2025
    Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 1 country.

Erin H SeeleyDepartment of Chemistry, University of Texas at Austin (E.H.S.).ORCID 0000-0002-8000-5754
Zhipeng LiuDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, IN (Z.L.).
Shuai YuanHeart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA (S.Y.).ORCID 0000-0002-9590-6555
Chad StroopeDepartment of Molecular and Cellular Physiology (C.S., N.A.R., L.F.D., D.K., A.W.O., O.R., C.B.P., A.Y.), LSU Health Sciences Center at Shreveport, LA.
Elizabeth CockerhamDepartment of Pathology and Translational Pathobiology (E.C., A.C.F., S.D., J.T., A.W.O., O.R., A.Y.), LSU Health Sciences Center at Shreveport, LA.ORCID 0000-0002-8549-1229
Nabil A RashdanDepartment of Molecular and Cellular Physiology (C.S., N.A.R., L.F.D., D.K., A.W.O., O.R., C.B.P., A.Y.), LSU Health Sciences Center at Shreveport, LA.ORCID 0000-0002-3356-6516
Luisa F DelgadilloDepartment of Molecular and Cellular Physiology (C.S., N.A.R., L.F.D., D.K., A.W.O., O.R., C.B.P., A.Y.), LSU Health Sciences Center at Shreveport, LA.ORCID 0000-0002-6580-1832
Alexandra C FinneyDepartment of Pathology and Translational Pathobiology (E.C., A.C.F., S.D., J.T., A.W.O., O.R., A.Y.), LSU Health Sciences Center at Shreveport, LA.ORCID 0000-0003-1575-4975
Dhananjay KumarDepartment of Molecular and Cellular Physiology (C.S., N.A.R., L.F.D., D.K., A.W.O., O.R., C.B.P., A.Y.), LSU Health Sciences Center at Shreveport, LA.
Sandeep DasDepartment of Pathology and Translational Pathobiology (E.C., A.C.F., S.D., J.T., A.W.O., O.R., A.Y.), LSU Health Sciences Center at Shreveport, LA.
Babak RazaniVascular Medicine Institute, Department of Medicine, University of Pittsburgh School of Medicine and UPMC, PA (B.R.).ORCID 0000-0002-7172-9240
Wanqing LiuDepartment of Pharmaceutical Sciences and Department of Pharmacology, Wayne State University, MI (W.L.).ORCID 0000-0001-7727-6900
James TraylorDepartment of Pathology and Translational Pathobiology (E.C., A.C.F., S.D., J.T., A.W.O., O.R., A.Y.), LSU Health Sciences Center at Shreveport, LA.ORCID 0000-0002-7119-6333
A Wayne OrrDepartment of Molecular and Cellular Physiology (C.S., N.A.R., L.F.D., D.K., A.W.O., O.R., C.B.P., A.Y.), LSU Health Sciences Center at Shreveport, LA.ORCID 0000-0002-2377-213X
Oren RomDepartment of Molecular and Cellular Physiology (C.S., N.A.R., L.F.D., D.K., A.W.O., O.R., C.B.P., A.Y.), LSU Health Sciences Center at Shreveport, LA.ORCID 0000-0002-9272-086X
Christopher B PattilloDepartment of Molecular and Cellular Physiology (C.S., N.A.R., L.F.D., D.K., A.W.O., O.R., C.B.P., A.Y.), LSU Health Sciences Center at Shreveport, LA.ORCID 0000-0002-8017-067X
Arif YurdagulDepartment of Molecular and Cellular Physiology (C.S., N.A.R., L.F.D., D.K., A.W.O., O.R., C.B.P., A.Y.), LSU Health Sciences Center at Shreveport, LA.ORCID 0000-0002-7613-6313
Louisiana State University Health Sciences Center Shreveport · USUniversity of Pittsburgh · USFlorida State University · USPurdue University West Lafayette · USThe University of Texas at Austin · US

Funding

THE ROLE OF MACROPHAGE LYSOSOMAL BIOGENESIS IN ATHEROSCLEROSISR01HL125838 · NHLBI · WASHINGTON UNIVERSITY · PI RAZANI, BABAK · 2015 to 2025
$4.6M
Dissecting the Impact of Dietary Protein on Macrophage mTOR Signaling and AtherosclerosisR01HL159461 · NHLBI · WASHINGTON UNIVERSITY · PI Bettina Mittendorfer, Babak Razani · 2022 to 2026
$3.3M
Harnessing macrophage lysosomal lipid metabolism in obesity-associated diseasesR01DK131188 · NIDDK · WASHINGTON UNIVERSITY · PI MITTENDORFER, BETTINA, RAZANI, BABAK · 2022 to 2025
$2.6M
Dysregulations in Polyamine Metabolism During AtherosclerosisR01HL167758 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI Arif Yurdagul · 2023 to 2026
$2.2M
Lipidated Amino Acids in Cardiometabolic DiseasesR01DK134011 · NIDDK · LOUISIANA STATE UNIV HSC SHREVEPORT · PI Oren Rom · 2022 to 2026
$2.1M
Fatty Acid Desaturase 1 (FADS1) Variants and Non-alcoholic Fatty Liver DiseaseR01DK106540 · NIDDK · WAYNE STATE UNIVERSITY · PI LIU, WANQING · 2016 to 2020
$1.9M
Cellular Reductive State Regulates ArteriogenesisR01HL139755 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI PATTILLO, CHRISTOPHER BRUCE · 2019 to 2023
$1.8M
A Precision Targeted Therapeutics for Nonalcoholic Fatty Liver DiseaseR01DK124612 · NIDDK · WAYNE STATE UNIVERSITY · PI LIU, WANQING · 2021 to 2024
$1.7M
Mechanisms of glycine-based therapy for atherosclerosisR00HL150233 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI ROM, OREN SHALOM · 2021 to 2023
$747k
Processing of Apoptotic Cell-Derived Cargo by Macrophages Continues Efferocytosis and Drives Atherosclerosis RegressionR00HL145131 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI YURDAGUL, ARIF · 2021 to 2023
$747k
Processing of Apoptotic Cell-Derived Cargo by Macrophages Continues Efferocytosis and Drives Atherosclerosis RegressionK99HL145131 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI YURDAGUL, ARIF · 2019 to 2020
$335k
Mechanisms of glycine-based therapy for atherosclerosisK99HL150233 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ROM, OREN SHALOM · 2020 to 2021
$207k
BLRD VA I01 BX003415NHLBI NIH HHS K99 HL145131NHLBI NIH HHS K99 HL150233NHLBI NIH HHS R00 HL145131NHLBI NIH HHS R00 HL150233NHLBI NIH HHS R01 HL125838NHLBI NIH HHS R01 HL139755NHLBI NIH HHS R01 HL159461NHLBI NIH HHS R01 HL167758NIDDK NIH HHS R01 DK106540NIDDK NIH HHS R01 DK124612NIDDK NIH HHS R01 DK131188NIDDK NIH HHS R01 DK134011
6 · The paper itself

Abstract

backgroundImpairments in carbohydrate, lipid, and amino acid metabolism drive features of plaque instability. However, where these impairments occur within the atheroma remains largely unknown. Therefore, we sought to characterize the spatial distribution of metabolites within stable and unstable atherosclerosis in both the fibrous cap and necrotic core.

methodsAtherosclerotic tissue specimens from 9 unmatched individuals were scored based on the Stary classification scale and subdivided into stable and unstable atheromas. After performing mass spectrometry imaging on these samples, we identified over 850 metabolite-related peaks. Using MetaboScape, METASPACE, and Human Metabolome Database, we confidently annotated 170 of these metabolites and found over 60 of these were different between stable and unstable atheromas. We then integrated these results with an RNA-sequencing data set comparing stable and unstable human atherosclerosis.

resultsUpon integrating our mass spectrometry imaging results with the RNA-sequencing data set, we discovered that pathways related to lipid metabolism and long-chain fatty acids were enriched in stable plaques, whereas reactive oxygen species, aromatic amino acid, and tryptophan metabolism were increased in unstable plaques. In addition, acylcarnitines and acylglycines were increased in stable plaques whereas tryptophan metabolites were enriched in unstable plaques. Evaluating spatial differences in stable plaques revealed lactic acid in the necrotic core, whereas pyruvic acid was elevated in the fibrous cap. In unstable plaques, 5-hydroxyindoleacetic acid was enriched in the fibrous cap.

conclusionsOur work here represents the first step to defining an atlas of metabolic pathways involved in plaque destabilization in human atherosclerosis. We anticipate this will be a valuable resource and open new avenues of research in cardiovascular disease.

Indexed as

AtherosclerosisPlaque, AtheroscleroticHumansMass SpectrometryNecrosisRNATryptophanRNATryptophanamino acidsatherosclerosiscardiovascular diseaseslipidsmass spectrometry

Identifiers

PMID37381983
PMCPMC10527524
OpenAlexW4382502272

What Socratic holds

Textmetadata
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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.