Evidence map›Paper›PMID 37850387›Full record

ArticleCirculation2023

Cellular Heterogeneity of Activated Primary Human Macrophages and Associated Drug-Gene Networks: From Biology to Precision Therapeutics.

Julius L Decano, Enrico Maiorino, Joan T Matamalas, Sarvesh Chelvanambi, Bart M Tiemeijer, Yoshihiro Yanagihara, Shin Mukai, Prabhash Kumar Jha, Diego V S Pestana, Edwin D'Souza and 8 more

Open access · hybridAbstract read
In one paragraph

Article in Circulation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

23 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Efferocytosis-associated Mrc1Frontiers in immunology · 2026
    Article
  7. Review
  8. Engineering Efferocytosis for Bone Regeneration.Macromolecular bioscience · 2025
    Review
  9. Article
  10. Progress in macrophage immune regulation of atherosclerosis.American journal of translational research · 2025
    Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
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  20. Review
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

18 authors at 1 institution in 1 country.

Julius L Decano *Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (J.L.D., J.T.M., S.C., B.M.T., Y.Y., S.M., D.V.S.P., E.D., M.W., R.G., T.A., A.S., S.A.S., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0003-0388-3585
Enrico Maiorino *Channing Division of Network Medicine (E.M., A.S., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-0159-4221
Joan T Matamalas *Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (J.L.D., J.T.M., S.C., B.M.T., Y.Y., S.M., D.V.S.P., E.D., M.W., R.G., T.A., A.S., S.A.S., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-7563-9269
Sarvesh Chelvanambi *Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (J.L.D., J.T.M., S.C., B.M.T., Y.Y., S.M., D.V.S.P., E.D., M.W., R.G., T.A., A.S., S.A.S., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0001-9621-0704
Bart M TiemeijerCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (J.L.D., J.T.M., S.C., B.M.T., Y.Y., S.M., D.V.S.P., E.D., M.W., R.G., T.A., A.S., S.A.S., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0001-6744-3226
Yoshihiro YanagiharaCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (J.L.D., J.T.M., S.C., B.M.T., Y.Y., S.M., D.V.S.P., E.D., M.W., R.G., T.A., A.S., S.A.S., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-6579-5567
Shin MukaiCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (J.L.D., J.T.M., S.C., B.M.T., Y.Y., S.M., D.V.S.P., E.D., M.W., R.G., T.A., A.S., S.A.S., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0009-0004-1350-001X
Prabhash Kumar JhaDepartment of Medicine, and Center for Excellence in Vascular Biology (P.K.J., P.L., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Diego V S PestanaCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (J.L.D., J.T.M., S.C., B.M.T., Y.Y., S.M., D.V.S.P., E.D., M.W., R.G., T.A., A.S., S.A.S., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-2226-2816
Edwin D'SouzaCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (J.L.D., J.T.M., S.C., B.M.T., Y.Y., S.M., D.V.S.P., E.D., M.W., R.G., T.A., A.S., S.A.S., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0003-4452-6285
Mary WhelanCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (J.L.D., J.T.M., S.C., B.M.T., Y.Y., S.M., D.V.S.P., E.D., M.W., R.G., T.A., A.S., S.A.S., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-0139-5572
Rile GeCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (J.L.D., J.T.M., S.C., B.M.T., Y.Y., S.M., D.V.S.P., E.D., M.W., R.G., T.A., A.S., S.A.S., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-5699-3561
Takaharu AsanoCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (J.L.D., J.T.M., S.C., B.M.T., Y.Y., S.M., D.V.S.P., E.D., M.W., R.G., T.A., A.S., S.A.S., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Amitabh SharmaCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (J.L.D., J.T.M., S.C., B.M.T., Y.Y., S.M., D.V.S.P., E.D., M.W., R.G., T.A., A.S., S.A.S., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Peter LibbyDepartment of Medicine, and Center for Excellence in Vascular Biology (P.K.J., P.L., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-1502-502X
Sasha A SinghCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (J.L.D., J.T.M., S.C., B.M.T., Y.Y., S.M., D.V.S.P., E.D., M.W., R.G., T.A., A.S., S.A.S., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0003-0929-3164
Elena AikawaCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (J.L.D., J.T.M., S.C., B.M.T., Y.Y., S.M., D.V.S.P., E.D., M.W., R.G., T.A., A.S., S.A.S., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0001-7835-2135
Masanori AikawaCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (J.L.D., J.T.M., S.C., B.M.T., Y.Y., S.M., D.V.S.P., E.D., M.W., R.G., T.A., A.S., S.A.S., E.A., M.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-9275-2079
Brigham and Women's Hospital · US

Funding

Pro-inflammatory activation of human macrophages regulated by lncRNAsR01HL149302 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, MASANORI · 2019 to 2022
$2.9M
PARP9 and PARP14 in atherosclerosisR01HL126901 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, MASANORI · 2016 to 2019
$2.4M
Linking endotype and phenotype to understand COPD heterogeneity via deep learning and network scienceK01HL166705 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Enrico Maiorino · 2023 to 2026
$713k
NHLBI NIH HHS K01 HL166705NHLBI NIH HHS R01 HL126901NHLBI NIH HHS R01 HL149302
6 · The paper itself

Abstract

backgroundInterferon-γ (IFNγ) signaling plays a complex role in atherogenesis. IFNγ stimulation of macrophages permits in vitro exploration of proinflammatory mechanisms and the development of novel immune therapies. We hypothesized that the study of macrophage subpopulations could lead to anti-inflammatory interventions.

methodsPrimary human macrophages activated by IFNγ (M(IFNγ)) underwent analyses by single-cell RNA sequencing, time-course cell-cluster proteomics, metabolite consumption, immunoassays, and functional tests (phagocytic, efferocytotic, and chemotactic). RNA-sequencing data were analyzed in LINCS (Library of Integrated Network-Based Cellular Signatures) to identify compounds targeting M(IFNγ) subpopulations. The effect of compound BI-2536 was tested in human macrophages in vitro and in a murine model of atherosclerosis.

resultsSingle-cell RNA sequencing identified 2 major clusters in M(IFNγ): inflammatory (M(IFNγ)

conclusionsWe characterized 2 clusters of macrophages in atherosclerosis and combined our cellular data with a cell-signature drug library to identify a novel compound that targets a subset of macrophages in atherosclerosis. Our approach is a precision medicine strategy to identify new drugs that target atherosclerosis and other inflammatory diseases.

Indexed as

AtherosclerosisPlaque, AtheroscleroticAnimalsBiologyGene Regulatory NetworksHumansMacrophagesMiceRNARNAatherosclerosisinflammationmacrophagesmultiomicsphagocytosissystems biology

Identifiers

PMID37850387
PMCPMC10624416
OpenAlexW4387729673

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.