Evidence map›Paper›PMID 37279475›Full record

ArticleEuropean heart journal2023

Cationic proteins from eosinophils bind bone morphogenetic protein receptors promoting vascular calcification and atherogenesis.

Zhaojie Meng, Shuya Zhang, Wei Li, Yunzhe Wang, Minjie Wang, Xin Liu, Cong-Lin Liu, Sha Liao, Tianxiao Liu, Chongzhe Yang and 11 more

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

Article in European heart journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
9.1field-weighted citation impact, top 2% 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

27 citing papers in PubMed, 38 citations in OpenAlex.

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  6. Emerging Mechanisms of Abdominal Aortic Aneurysm.Current atherosclerosis reports · 2026
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 6 institutions in 3 countries.

Zhaojie MengDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA.
Shuya ZhangDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA.
Wei LiCollege of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, Jilin, China.
Yunzhe WangDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA.
Minjie WangDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA.
Xin LiuDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA.
Cong-Lin LiuDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA.ORCID 0000-0002-0156-1446
Sha LiaoDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA.
Tianxiao LiuDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA.ORCID 0000-0001-5050-8804
Chongzhe YangDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA.
Jes S LindholtDepartment of Cardiothoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark.
Lars M RasmussenElite Research Centre of Individualized Treatment for Arterial Disease, University Hospital, Odense, Denmark.
Lasse M ObelElite Research Centre of Individualized Treatment for Arterial Disease, University Hospital, Odense, Denmark.
Jane StubbeCardiovascular and Renal Research unit, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Axel C DiederichsenElite Research Centre of Individualized Treatment for Arterial Disease, University Hospital, Odense, Denmark.ORCID 0000-0002-1285-4826
Yong SunDepartment of Pathology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Yabing ChenDepartment of Pathology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Paul B YuDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA.
Peter LibbyDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA.
Guo-Ping ShiDepartment of Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Boston, MA 02115, USA.ORCID 0000-0001-5809-2567
Junli GuoHainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research & Key Laboratory of Emergency and Trauma of Ministry of Education, Institute of Cardiovascular Research of the First Affiliated Hospital, Hainan Medical University, Haikou 571199, Hainan, China.ORCID 0000-0002-9740-9819
Brigham and Women's Hospital · USOdense University Hospital · DKUniversity of Alabama at Birmingham · USHainan Medical University · CNJilin Agricultural University · CNUniversity of Southern Denmark · DK

Funding

Role of Mast cells in Alzheimer's DiseaseR01AG063839 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI LIBBY, PETER · 2020 to 2024
$3.1M
Molecular Mechanisms Governing Vascular Cell Function and Phenotype in Health and DiseaseR01HL158097 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI CHEN, HONG, CHEN, YABING · 2021 to 2024
$3.0M
Protein Arginine Methylation in Vascular Smooth Muscle Cell Phenotypic Modulation and CalcificationR01HL167201 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Yabing Chen, Xinyang Zhao · 2023 to 2026
$2.8M
Role of group 2 innate lymphoid cells in myocardial infarctionR01HL157073 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LIBBY, PETER · 2022 to 2025
$2.7M
Role of ILC2 and eosinophils in abdominal aortic aneurysmR01HL151627 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LIBBY, PETER · 2021 to 2024
$2.7M
Mechanisms and Modulation of Accelerated Atherosclerosis in Clonal HematopoiesisR01HL163099 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LIBBY, PETER · 2022 to 2025
$2.6M
Regulation of vascular smooth muscle cell function in atherosclerosisR01HL136165 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CHEN, YABING · 2017 to 2020
$2.1M
Novel regulation of vascular dementiaR01AG082839 · NIA · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Yabing Chen · 2023 to 2026
$2.1M
Novel mechanisms of the thrombotic complications of atherosclerosisR01HL134892 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LIBBY, PETER · 2019 to 2022
$1.7M
BLRD VA I01 BX004426NHLBI NIH HHS HL151627NHLBI NIH HHS R01 HL134892NHLBI NIH HHS R01 HL136165NHLBI NIH HHS R01 HL151627NHLBI NIH HHS R01 HL157073NHLBI NIH HHS R01 HL158097NHLBI NIH HHS R01 HL163099NHLBI NIH HHS R01 HL167201NIA NIH HHS R01 AG063839NIA NIH HHS R01 AG082839NIH HHS AG063839
6 · The paper itself

Abstract

aimsBlood eosinophil count and eosinophil cationic protein (ECP) concentration are risk factors of cardiovascular diseases. This study tested whether and how eosinophils and ECP contribute to vascular calcification and atherogenesis. METHODS AND

resultsImmunostaining revealed eosinophil accumulation in human and mouse atherosclerotic lesions. Eosinophil deficiency in ΔdblGATA mice slowed atherogenesis with increased lesion smooth muscle cell (SMC) content and reduced calcification. This protection in ΔdblGATA mice was muted when mice received donor eosinophils from wild-type (WT), Il4-/-, and Il13-/- mice or mouse eosinophil-associated-ribonuclease-1 (mEar1), a murine homologue of ECP. Eosinophils or mEar1 but not interleukin (IL) 4 or IL13 increased the calcification of SMC from WT mice but not those from Runt-related transcription factor-2 (Runx2) knockout mice. Immunoblot analyses showed that eosinophils and mEar1 activated Smad-1/5/8 but did not affect Smad-2/3 activation or expression of bone morphogenetic protein receptors (BMPR-1A/1B/2) or transforming growth factor (TGF)-β receptors (TGFBR1/2) in SMC from WT and Runx2 knockout mice. Immunoprecipitation showed that mEar1 formed immune complexes with BMPR-1A/1B but not TGFBR1/2. Immunofluorescence double-staining, ligand binding, and Scatchard plot analysis demonstrated that mEar1 bound to BMPR-1A and BMPR-1B with similar affinity. Likewise, human ECP and eosinophil-derived neurotoxin (EDN) also bound to BMPR-1A/1B on human vascular SMC and promoted SMC osteogenic differentiation. In a cohort of 5864 men from the Danish Cardiovascular Screening trial and its subpopulation of 394 participants, blood eosinophil counts and ECP levels correlated with the calcification scores of different arterial segments from coronary arteries to iliac arteries.

conclusionEosinophils release cationic proteins that can promote SMC calcification and atherogenesis using the BMPR-1A/1B-Smad-1/5/8-Runx2 signalling pathway.

Indexed as

AtherosclerosisVascular CalcificationAnimalsBlood ProteinsBone Morphogenetic Protein ReceptorsCore Binding Factor Alpha 1 SubunitEosinophil Granule ProteinsEosinophilsHumansInterleukin-13MaleMiceMice, KnockoutOsteogenesisRibonucleasesBlood ProteinsBone Morphogenetic Protein ReceptorsCore Binding Factor Alpha 1 SubunitEosinophil Granule ProteinsInterleukin-13RibonucleasesBone morphogenetic protein receptorsCalcificationEosinophilEosinophil cationic proteinSmooth muscle cell

Identifiers

PMID37279475
PMCPMC10393071
OpenAlexW4379600471

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Registered trials

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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.