Evidence map›Paper›PMID 40438929›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2025

Multiomic Landscape of Extracellular Vesicles in Human Carotid Atherosclerotic Plaque Reveals Endothelial Communication Networks.

Sneha Raju, Mandy E Turner, Christian Cao, Majed Abdul-Samad, Neil Punwasi, Mark C Blaser, Rachel M E Cahalane, Steven R Botts, Kamalben Prajapati, Sarvatit Patel and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Sneha RajuToronto General Hospital Research Institute, University Health Network, ON, Toronto, Canada (S.R., S.R.B., K.P., S.P., R.W., D.G., J.E.F., K.L.H.).ORCID 0000-0001-9149-5907
Mandy E TurnerCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.E.T., M.C.B., R.M.E.C., S.A.S., E.A.).
Christian CaoTemerty Faculty of Medicine, University of Toronto, ON, Canada (S.R., C.C., S.R.B., L.F., K.L.H.).ORCID 0000-0002-0395-0381
Majed Abdul-SamadDepartment of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada (M.A.-S., K.P., R.W., J.E.F., K.L.H.).ORCID 0009-0006-6007-3190
Neil PunwasiPeter Munk Cardiac Centre, University Health Network, Toronto, Canada (N.P., M.A.S., V.S., J.E.F., K.L.H.).ORCID 0009-0004-9555-650X
Mark C BlaserCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.E.T., M.C.B., R.M.E.C., S.A.S., E.A.).ORCID 0000-0002-3923-9786
Rachel M E CahalaneCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.E.T., M.C.B., R.M.E.C., S.A.S., E.A.).ORCID 0000-0003-4017-0592
Steven R BottsToronto General Hospital Research Institute, University Health Network, ON, Toronto, Canada (S.R., S.R.B., K.P., S.P., R.W., D.G., J.E.F., K.L.H.).ORCID 0000-0002-2420-4679
Kamalben PrajapatiToronto General Hospital Research Institute, University Health Network, ON, Toronto, Canada (S.R., S.R.B., K.P., S.P., R.W., D.G., J.E.F., K.L.H.).
Sarvatit PatelToronto General Hospital Research Institute, University Health Network, ON, Toronto, Canada (S.R., S.R.B., K.P., S.P., R.W., D.G., J.E.F., K.L.H.).ORCID 0000-0002-3101-8380
Ruilin WuToronto General Hospital Research Institute, University Health Network, ON, Toronto, Canada (S.R., S.R.B., K.P., S.P., R.W., D.G., J.E.F., K.L.H.).
Dakota GustafsonToronto General Hospital Research Institute, University Health Network, ON, Toronto, Canada (S.R., S.R.B., K.P., S.P., R.W., D.G., J.E.F., K.L.H.).ORCID 0000-0001-8374-6331
Natalie J GalantPrincess Margaret Cancer Center, Toronto, ON, Canada (N.J.G.).ORCID 0000-0001-8923-5794
Lindsey FiddesTemerty Faculty of Medicine, University of Toronto, ON, Canada (S.R., C.C., S.R.B., L.F., K.L.H.).ORCID 0009-0009-1183-6114
Melody ChemalyVascular Surgery Division, Department of Molecular Medicine and Surgery, Karolinska University Hospital and Karolinska Institut, Stockholm, Sweden (M.C., U.H., L.M.).ORCID 0000-0001-6211-7595
Ulf HedinVascular Surgery Division, Department of Molecular Medicine and Surgery, Karolinska University Hospital and Karolinska Institut, Stockholm, Sweden (M.C., U.H., L.M.).ORCID 0000-0001-9212-3945
Ljubica MaticVascular Surgery Division, Department of Molecular Medicine and Surgery, Karolinska University Hospital and Karolinska Institut, Stockholm, Sweden (M.C., U.H., L.M.).ORCID 0000-0002-7294-9667
Michael A SeidmanPeter Munk Cardiac Centre, University Health Network, Toronto, Canada (N.P., M.A.S., V.S., J.E.F., K.L.H.).ORCID 0000-0002-9594-827X
Vallijah SubasriPeter Munk Cardiac Centre, University Health Network, Toronto, Canada (N.P., M.A.S., V.S., J.E.F., K.L.H.).ORCID 0000-0002-6584-877X
Sasha A SinghCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.E.T., M.C.B., R.M.E.C., S.A.S., E.A.).ORCID 0000-0003-0929-3164
Elena AikawaCenter for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.E.T., M.C.B., R.M.E.C., S.A.S., E.A.).ORCID 0000-0001-7835-2135
Jason E FishToronto General Hospital Research Institute, University Health Network, ON, Toronto, Canada (S.R., S.R.B., K.P., S.P., R.W., D.G., J.E.F., K.L.H.).ORCID 0000-0003-0640-7277
Kathryn L HoweToronto General Hospital Research Institute, University Health Network, ON, Toronto, Canada (S.R., S.R.B., K.P., S.P., R.W., D.G., J.E.F., K.L.H.).ORCID 0000-0002-6519-2280

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCarotid atherosclerosis is orchestrated by cell-cell communication that drives progression along a clinical continuum (asymptomatic to symptomatic). Extracellular vesicles (EVs) are cell-derived nanoparticles representing a new paradigm in cellular communication. Little is known about their biological cargo, cellular origin/destination, and functional roles in human atherosclerotic plaque.

methodsEVs were enriched via size exclusion chromatography from human carotid endarterectomy samples dissected into paired plaque and marginal zones (symptomatic n=16, asymptomatic n=13). EV-cargos were assessed via whole transcriptome microRNA-sequencing and mass spectrometry-based proteomics. EV multiomics was integrated with bulk and single-cell RNA-sequencing datasets to predict EV cellular origin and ligand-receptor interactions, and multimodal biological network integration of EV-cargo was completed. EV functional impact was assessed with endothelial angiogenesis assays.

resultsCarotid plaques contained more EVs than adjacent marginal zones, with differential enrichment for EV-microRNAs and EV-proteins in key atherogenic pathways. EV cellular origin analysis suggested that tissue EV signatures originated from endothelial cells, smooth muscle cells, and immune cells. Integrated tissue vesiculomics and single-cell RNA-sequencing indicated complex EV-vascular cell communication that changed with disease progression and plaque vulnerability (ie, symptomatic disease). Plaques from symptomatic patients, but not asymptomatic patients, were characterized by increased involvement of endothelial pathways and more complex ligand-receptor interactions, relative to their marginal zones. Plaque EVs were predicted to mediate communication with endothelial cells. Pathway enrichment analysis delineated an endothelial signature with roles in angiogenesis and neovascularization, well-known indices of plaque instability. This was validated functionally, wherein human carotid symptomatic plaque EVs induced sprouting angiogenesis in comparison to their matched marginal zones.

conclusionsOur findings indicate that EVs may drive dynamic changes in plaques through EV-vascular cell communication and effector functions that typify vulnerability to rupture, precipitating symptomatic disease. The discovery of endothelial-directed angiogenic processes mediated by EVs creates new therapeutic avenues for atherosclerosis.

Indexed as

Carotid Artery DiseasesCell CommunicationEndothelial CellsExtracellular VesiclesPlaque, AtheroscleroticAgedEndarterectomy, CarotidFemaleHumansMaleMicroRNAsMiddle AgedNeovascularization, PathologicProteomicsTranscriptomeMicroRNAsatherosclerosisendothelial cellsextracellular vesiclesmicroRNAsproteomics

Identifiers

PMID40438929
PMCPMC12188822

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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.