Evidence map›Paper›PMID 37427430›Full record

ArticleCirculation2023

Multiomics of Tissue Extracellular Vesicles Identifies Unique Modulators of Atherosclerosis and Calcific Aortic Valve Stenosis.

Mark C Blaser, Fabrizio Buffolo, Arda Halu, Mandy E Turner, Florian Schlotter, Hideyuki Higashi, Lorena Pantano, Cassandra L Clift, Louis A Saddic, Samantha K Atkins and 13 more

Open access · bronzeAbstract 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 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
11.5field-weighted citation impact, top 1% 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

67 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.

  1. Pooled it
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  8. Aortic Stenosis Hyalectan Remodeling Revealed by Proteomics and Glycoproteomics.Arteriosclerosis, thrombosis, and vascular biology · 2026
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7 more citing papers are in PubMed but not listed here.

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

23 authors at 7 institutions in 3 countries.

Mark C BlaserCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine (M.C.B., F.B., A.H., M.E.T., F.S., H.H., C.L.C., L.A.S., S.K.A., M.A.R., T.P., S.A.S., M.A., E.A.).ORCID 0000-0002-3923-9786
Fabrizio BuffoloCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine (M.C.B., F.B., A.H., M.E.T., F.S., H.H., C.L.C., L.A.S., S.K.A., M.A.R., T.P., S.A.S., M.A., E.A.).
Arda HaluCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine (M.C.B., F.B., A.H., M.E.T., F.S., H.H., C.L.C., L.A.S., S.K.A., M.A.R., T.P., S.A.S., M.A., E.A.).ORCID 0000-0001-6217-790X
Mandy E TurnerCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine (M.C.B., F.B., A.H., M.E.T., F.S., H.H., C.L.C., L.A.S., S.K.A., M.A.R., T.P., S.A.S., M.A., E.A.).
Florian SchlotterCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine (M.C.B., F.B., A.H., M.E.T., F.S., H.H., C.L.C., L.A.S., S.K.A., M.A.R., T.P., S.A.S., M.A., E.A.).ORCID 0000-0003-4840-1172
Hideyuki HigashiCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine (M.C.B., F.B., A.H., M.E.T., F.S., H.H., C.L.C., L.A.S., S.K.A., M.A.R., T.P., S.A.S., M.A., E.A.).
Lorena PantanoT H Chan School of Public Health, Harvard University, Boston, MA (L.P.).ORCID 0000-0002-3859-3249
Cassandra L CliftCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine (M.C.B., F.B., A.H., M.E.T., F.S., H.H., C.L.C., L.A.S., S.K.A., M.A.R., T.P., S.A.S., M.A., E.A.).ORCID 0000-0003-2441-4251
Louis A SaddicCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine (M.C.B., F.B., A.H., M.E.T., F.S., H.H., C.L.C., L.A.S., S.K.A., M.A.R., T.P., S.A.S., M.A., E.A.).
Samantha K AtkinsCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine (M.C.B., F.B., A.H., M.E.T., F.S., H.H., C.L.C., L.A.S., S.K.A., M.A.R., T.P., S.A.S., M.A., E.A.).
Maximillian A RogersCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine (M.C.B., F.B., A.H., M.E.T., F.S., H.H., C.L.C., L.A.S., S.K.A., M.A.R., T.P., S.A.S., M.A., E.A.).
Tan PhamCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine (M.C.B., F.B., A.H., M.E.T., F.S., H.H., C.L.C., L.A.S., S.K.A., M.A.R., T.P., S.A.S., M.A., E.A.).
Amélie VrommanChanning Division of Network Medicine, Department of Medicine (A.H., M.A.).ORCID 0000-0002-1724-2095
Eugenia ShvartzChanning Division of Network Medicine, Department of Medicine (A.H., M.A.).
Galina K SukhovaChanning Division of Network Medicine, Department of Medicine (A.H., M.A.).ORCID 0000-0002-1421-9455
Silvia MonticoneDivision of Internal Medicine and Hypertension (S.M.), University of Torino, Italy.ORCID 0000-0002-7322-2005
Giovanni CamussiDepartment of Medical Sciences (G.C.), University of Torino, Italy.
Simon C RobsonCenter for Inflammation Research, Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (S.C.R.).
Simon C BodyBoston University School of Medicine, Boston, MA (S.C.B.).ORCID 0000-0001-6721-7050
Jochen D MuehlschlegelCenter for Perioperative Genomics, Department of Anesthesiology, Perioperative and Pain Medicine (J.D.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Sasha A SinghCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine (M.C.B., F.B., A.H., M.E.T., F.S., H.H., C.L.C., L.A.S., S.K.A., M.A.R., T.P., S.A.S., M.A., E.A.).ORCID 0000-0003-0929-3164
Masanori AikawaCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine (M.C.B., F.B., A.H., M.E.T., F.S., H.H., C.L.C., L.A.S., S.K.A., M.A.R., T.P., S.A.S., M.A., E.A.).ORCID 0000-0002-9275-2079
Elena AikawaCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine (M.C.B., F.B., A.H., M.E.T., F.S., H.H., C.L.C., L.A.S., S.K.A., M.A.R., T.P., S.A.S., M.A., E.A.).ORCID 0000-0001-7835-2135
Center for Excellence in Education · USBeth Israel Deaconess Medical Center · USBoston University · USBrigham and Women's Hospital · USDepartment of Medical Sciences · BYEuropean Society of Hypertension · ITHarvard University · US

Funding

The Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0M
Improving Mitral Compensation In Ischemic RegurgitationR01HL141917 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI AIKAWA, ELENA, BISCHOFF, JOYCE E. · 2018 to 2021
$5.6M
Molecular Determinants of Arterial Remodeling in AtherogenesisR01HL080472 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LIBBY, PETER · 2005 to 2018
$5.0M
Cardiac Exosomes in myocardial Ischemic injuryR01HL150401 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MUEHLSCHLEGEL, JOCHEN DANIEL · 2020 to 2024
$3.3M
Genomics of Post-Operative Atrial Fibrillation After Cardiac SurgeryR01HL149998 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MUEHLSCHLEGEL, JOCHEN DANIEL, STRANGER, BARBARA E · 2021 to 2024
$3.1M
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
Novel mechanisms of the thrombotic complications of atherosclerosisR01HL134892 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LIBBY, PETER · 2019 to 2022
$1.7M
Integrative network-based analysis of multi-omics data to elucidate the molecular connection between asthma and COPDK25HL150336 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI HALU, ARDA · 2020 to 2024
$945k
NCATS NIH HHS UL1 TR002541NHLBI NIH HHS K25 HL150336NHLBI NIH HHS R01 HL080472NHLBI NIH HHS R01 HL134892NHLBI NIH HHS R01 HL136431NHLBI NIH HHS R01 HL141917NHLBI NIH HHS R01 HL147095NHLBI NIH HHS R01 HL149998NHLBI NIH HHS R01 HL150401
6 · The paper itself

Abstract

backgroundFewer than 50% of patients who develop aortic valve calcification have concomitant atherosclerosis, implying differential pathogenesis. Although circulating extracellular vesicles (EVs) act as biomarkers of cardiovascular diseases, tissue-entrapped EVs are associated with early mineralization, but their cargoes, functions, and contributions to disease remain unknown.

methodsDisease stage-specific proteomics was performed on human carotid endarterectomy specimens (n=16) and stenotic aortic valves (n=18). Tissue EVs were isolated from human carotid arteries (normal, n=6; diseased, n=4) and aortic valves (normal, n=6; diseased, n=4) by enzymatic digestion, (ultra)centrifugation, and a 15-fraction density gradient validated by proteomics, CD63-immunogold electron microscopy, and nanoparticle tracking analysis. Vesiculomics, comprising vesicular proteomics and small RNA-sequencing, was conducted on tissue EVs. TargetScan identified microRNA targets. Pathway network analyses prioritized genes for validation in primary human carotid artery smooth muscle cells and aortic valvular interstitial cells.

resultsDisease progression drove significant convergence (

conclusionsThe first comparative proteomics study of human carotid artery plaques and calcified aortic valves identifies unique drivers of atherosclerosis versus aortic valve stenosis and implicates EVs in advanced cardiovascular calcification. We delineate a vesiculomics strategy to isolate, purify, and study protein and RNA cargoes from EVs entrapped in fibrocalcific tissues. Integration of vesicular proteomics and transcriptomics by network approaches revealed novel roles for tissue EVs in modulating cardiovascular disease.

Indexed as

Aortic Valve StenosisAtherosclerosisCalcinosisExtracellular VesiclesMicroRNAsAortic ValveCells, CulturedHumansMultiomicsWnt Signaling PathwayMicroRNAsaortic valve stenosisatherosclerosisextracellular vesiclesmicroRNAsproteomics

Identifiers

PMID37427430
PMCPMC10527599
OpenAlexW4383710497

What Socratic 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 Socratic graph.