Evidence map›Paper›PMID 32460581›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2020

S100A9-RAGE Axis Accelerates Formation of Macrophage-Mediated Extracellular Vesicle Microcalcification in Diabetes Mellitus.

Ryo Kawakami, Shunsuke Katsuki, Richard Travers, Dayanna Carolina Romero, Dakota Becker-Greene, Livia Silva Araujo Passos, Hideyuki Higashi, Mark C Blaser, Galina K Sukhova, Josef Buttigieg and 10 more

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
7.1field-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

60 citing papers in PubMed, 89 citations in OpenAlex.

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  15. Considerations on the Development of Therapeutics in Vascular Calcification.Journal of cardiovascular development and disease · 2025
    Review
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  17. [Advances in Animal Modeling in the Study of Bone-Vascular Axis Comorbidities].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 6 institutions in 3 countries.

Ryo KawakamiFrom the Center for Excellence in Vascular Biology (R.K., S.K., R.T., D.C.R., D.B.-G., L.S.A.P., G.K.S., P.L., M.A., K.C., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Shunsuke KatsukiFrom the Center for Excellence in Vascular Biology (R.K., S.K., R.T., D.C.R., D.B.-G., L.S.A.P., G.K.S., P.L., M.A., K.C., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Richard TraversFrom the Center for Excellence in Vascular Biology (R.K., S.K., R.T., D.C.R., D.B.-G., L.S.A.P., G.K.S., P.L., M.A., K.C., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Dayanna Carolina RomeroFrom the Center for Excellence in Vascular Biology (R.K., S.K., R.T., D.C.R., D.B.-G., L.S.A.P., G.K.S., P.L., M.A., K.C., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Dakota Becker-GreeneFrom the Center for Excellence in Vascular Biology (R.K., S.K., R.T., D.C.R., D.B.-G., L.S.A.P., G.K.S., P.L., M.A., K.C., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Livia Silva Araujo PassosFrom the Center for Excellence in Vascular Biology (R.K., S.K., R.T., D.C.R., D.B.-G., L.S.A.P., G.K.S., P.L., M.A., K.C., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Hideyuki HigashiCenter for Interdisciplinary Cardiovascular Sciences (H.H., M.C.B., S.A.S., M.A., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Mark C BlaserCenter for Interdisciplinary Cardiovascular Sciences (H.H., M.C.B., S.A.S., M.A., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Galina K SukhovaFrom the Center for Excellence in Vascular Biology (R.K., S.K., R.T., D.C.R., D.B.-G., L.S.A.P., G.K.S., P.L., M.A., K.C., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Josef ButtigiegDepartment of Biology, University of Regina, Saskatchewan, Canada (J.B.).
David KoprivaRegina Qu'Appelle Health Region, University of Saskatchewan, Regina, Canada (D.K.).
Ann Marie SchmidtDiabetes Research Program, Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, New York University (A.M.S.).
Daniel G AndersonInstitutes for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge (D.G.A.).
Sasha A SinghCenter for Interdisciplinary Cardiovascular Sciences (H.H., M.C.B., S.A.S., M.A., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Luis CardosoDepartment of Biomedical Engineering, The City College of New York (L.C., S.W.).
Sheldon WeinbaumDepartment of Biomedical Engineering, The City College of New York (L.C., S.W.).
Peter LibbyFrom the Center for Excellence in Vascular Biology (R.K., S.K., R.T., D.C.R., D.B.-G., L.S.A.P., G.K.S., P.L., M.A., K.C., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Masanori AikawaFrom the Center for Excellence in Vascular Biology (R.K., S.K., R.T., D.C.R., D.B.-G., L.S.A.P., G.K.S., P.L., M.A., K.C., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Kevin CroceFrom the Center for Excellence in Vascular Biology (R.K., S.K., R.T., D.C.R., D.B.-G., L.S.A.P., G.K.S., P.L., M.A., K.C., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Elena AikawaFrom the Center for Excellence in Vascular Biology (R.K., S.K., R.T., D.C.R., D.B.-G., L.S.A.P., G.K.S., P.L., M.A., K.C., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Brigham and Women's Hospital · USCity College of New York · USMassachusetts Institute of Technology · USNew York University · USRegina Qu'Appelle Health Region · CAUniversity of Regina · CA

Funding

Improving Mitral Compensation In Ischemic RegurgitationR01HL141917 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI AIKAWA, ELENA, BISCHOFF, JOYCE E. · 2018 to 2021
$5.6M
Macrophage-derived microcalcificaitonsR01HL136431 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, ELENA · 2017 to 2020
$2.7M
New driver of fibrosis and calcification in CAVDR01HL147095 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, ELENA · 2019 to 2022
$2.4M
NHLBI NIH HHS R01 HL136431NHLBI NIH HHS R01 HL141917NHLBI NIH HHS R01 HL147095
6 · The paper itself

Abstract

objectiveVascular calcification is a cardiovascular risk factor and accelerated in diabetes mellitus. Previous work has established a role for calcification-prone extracellular vesicles in promoting vascular calcification. However, the mechanisms by which diabetes mellitus provokes cardiovascular events remain incompletely understood. Our goal was to identify that increased S100A9 promotes the release of calcification-prone extracellular vesicles from human macrophages in diabetes mellitus. Approach and Results: Human primary macrophages exposed to high glucose (25 mmol/L) increased S100A9 secretion and the expression of receptor for advanced glycation end products (RAGE) protein. Recombinant S100A9 induced the expression of proinflammatory and osteogenic factors, as well as the number of extracellular vesicles with high calcific potential (alkaline phosphatase activity,

conclusionsUnder hyperglycemic conditions, macrophages release calcific extracellular vesicles through mechanisms involving the S100A9-RAGE axis, thus contributing to the formation of microcalcification within atherosclerotic plaques.

Indexed as

AnimalsCalgranulin BDiabetes ComplicationsDiabetes Mellitus, ExperimentalExtracellular VesiclesHumansMacrophage ActivationMacrophagesMiceMice, Inbred C57BLPlaque, AtheroscleroticReceptor for Advanced Glycation End ProductsVascular CalcificationCalgranulin BReceptor for Advanced Glycation End Productsatherosclerosisdiabetes mellitusextracellular vesiclesmacrophagesvascular calcification

Identifiers

PMID32460581
PMCPMC7377960
OpenAlexW3032452569

What OpenQuestion holds

Textmetadata
LicenceTDM
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.