Evidence map›Paper›PMID 33147993›Full record

Observational studyArteriosclerosis, thrombosis, and vascular biology2021

Altered Macrophage Polarization Induces Experimental Pulmonary Hypertension and Is Observed in Patients With Pulmonary Arterial Hypertension.

Amira Zawia, Nadine D Arnold, Laura West, Josephine A Pickworth, Helena Turton, James Iremonger, Adam T Braithwaite, Jaime Cañedo, Simon A Johnston, A A Roger Thompson and 2 more

Open access · hybridAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Arteriosclerosis, thrombosis, and vascular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.3field-weighted citation impact, top 4% 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

47 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
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  7. Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025
    Review
  8. Vascular Remodeling: The Multicellular Mechanisms of Pulmonary Hypertension.International journal of molecular sciences · 2025
    Review
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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

12 authors at 2 institutions in 2 countries.

Amira ZawiaDepartment of Infection, Immunity and Cardiovascular Disease (A.Z., N.D.A., L.W., J.A.P., H.T., J.I., A.T.B., J.C., S.A.J., A.A.R.T., A.L.), University of Sheffield, United Kingdom.
Nadine D ArnoldDepartment of Infection, Immunity and Cardiovascular Disease (A.Z., N.D.A., L.W., J.A.P., H.T., J.I., A.T.B., J.C., S.A.J., A.A.R.T., A.L.), University of Sheffield, United Kingdom.
Laura WestDepartment of Infection, Immunity and Cardiovascular Disease (A.Z., N.D.A., L.W., J.A.P., H.T., J.I., A.T.B., J.C., S.A.J., A.A.R.T., A.L.), University of Sheffield, United Kingdom.
Josephine A PickworthDepartment of Infection, Immunity and Cardiovascular Disease (A.Z., N.D.A., L.W., J.A.P., H.T., J.I., A.T.B., J.C., S.A.J., A.A.R.T., A.L.), University of Sheffield, United Kingdom.
Helena TurtonDepartment of Infection, Immunity and Cardiovascular Disease (A.Z., N.D.A., L.W., J.A.P., H.T., J.I., A.T.B., J.C., S.A.J., A.A.R.T., A.L.), University of Sheffield, United Kingdom.
James IremongerDepartment of Infection, Immunity and Cardiovascular Disease (A.Z., N.D.A., L.W., J.A.P., H.T., J.I., A.T.B., J.C., S.A.J., A.A.R.T., A.L.), University of Sheffield, United Kingdom.
Adam T BraithwaiteDepartment of Infection, Immunity and Cardiovascular Disease (A.Z., N.D.A., L.W., J.A.P., H.T., J.I., A.T.B., J.C., S.A.J., A.A.R.T., A.L.), University of Sheffield, United Kingdom.
Jaime CañedoDepartment of Infection, Immunity and Cardiovascular Disease (A.Z., N.D.A., L.W., J.A.P., H.T., J.I., A.T.B., J.C., S.A.J., A.A.R.T., A.L.), University of Sheffield, United Kingdom.
Simon A JohnstonDepartment of Infection, Immunity and Cardiovascular Disease (A.Z., N.D.A., L.W., J.A.P., H.T., J.I., A.T.B., J.C., S.A.J., A.A.R.T., A.L.), University of Sheffield, United Kingdom.
A A Roger ThompsonDepartment of Infection, Immunity and Cardiovascular Disease (A.Z., N.D.A., L.W., J.A.P., H.T., J.I., A.T.B., J.C., S.A.J., A.A.R.T., A.L.), University of Sheffield, United Kingdom.
Gaynor MillerDepartment of Oncology and Metabolism (G.M.), University of Sheffield, United Kingdom.
Allan LawrieDepartment of Infection, Immunity and Cardiovascular Disease (A.Z., N.D.A., L.W., J.A.P., H.T., J.I., A.T.B., J.C., S.A.J., A.A.R.T., A.L.), University of Sheffield, United Kingdom.
Anna Needs Neuroblastoma Answers · USBirmingham Dental Hospital · GB

Funding

British Heart Foundation FS/18/52/33808
6 · The paper itself

Abstract

objectiveTo determine whether global reduction of CD68 (cluster of differentiation) macrophages impacts the development of experimental pulmonary arterial hypertension (PAH) and whether this reduction affects the balance of pro- and anti-inflammatory macrophages within the lung. Additionally, to determine whether there is evidence of an altered macrophage polarization in patients with PAH. Approach and Results: Macrophage reduction was induced in mice via doxycycline-induced CD68-driven cytotoxic diphtheria toxin A chain expression (macrophage low [MacLow] mice). Chimeric mice were generated using bone marrow transplant. Mice were phenotyped for PAH by echocardiography and closed chest cardiac catheterization. Murine macrophage phenotyping was performed on lungs, bone marrow-derived macrophages, and alveolar macrophages using immunohistochemical and flow cytometry. Monocyte-derived macrophages were isolated from PAH patients and healthy volunteers and polarization capacity assessed morphologically and by flow cytometry. After 6 weeks of macrophage depletion, male but not female MacLow mice developed PAH. Chimeric mice demonstrated a requirement for both MacLow bone marrow and MacLow recipient mice to cause PAH. Immunohistochemical analysis of lung sections demonstrated imbalance in M1/M2 ratio in male MacLow mice only, suggesting that this imbalance may drive the PAH phenotype. M1/M2 imbalance was also seen in male MacLow bone marrow-derived macrophages and PAH patient monocyte-derived macrophages following stimulation with doxycycline and IL (interleukin)-4, respectively. Furthermore, MacLow-derived alveolar macrophages showed characteristic differences in terms of their polarization and expression of diphtheria toxin A chain following stimulation with doxycycline.

conclusionsThese data further highlight a sex imbalance in PAH and further implicate immune cells into this paradigm. Targeting imbalance of macrophage population may offer a future therapeutic option.

Indexed as

Macrophage ActivationVascular RemodelingAdultAgedAnimalsAntigens, CDAntigens, Differentiation, MyelomonocyticCase-Control StudiesCD68 MoleculeCell ProliferationDiphtheria ToxinDisease Models, AnimalFemaleHumansHypoxiaMacrophages, AlveolarAntigens, CDAntigens, Differentiation, MyelomonocyticCD68 antigen, humanCD68 MoleculeDiphtheria Toxindiphtheria toxin fragment APeptide Fragmentsheart failure, righthumansmacrophagesmodels, animalpulmonary hypertension

Identifiers

PMID33147993
PMCPMC7752239
OpenAlexW3097958875

What OpenQuestion holds

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LicenceCC BY-NC
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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.