Evidence map›Paper›PMID 38174557›Full record

ArticleCirculation research2024

Directional Endothelial Communication by Polarized Extracellular Vesicle Release.

Sneha Raju, Steven R Botts, Mark C Blaser, Majed Abdul-Samad, Kamalben Prajapati, Negar Khosraviani, Tse Wing Winnie Ho, Leandro C D Breda, Crizza Ching, Natalie J Galant and 9 more

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

Article in Circulation research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

19 citing papers in PubMed, 19 citations in OpenAlex.

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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

19 authors at 5 institutions in 2 countries.

Sneha RajuToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada (S.R., S.R.B., M.A.-S., K.P., N.K., L.C.D.B., C.C., R.W., J.E.F., K.L.H.).ORCID 0000-0001-9149-5907
Steven R BottsToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada (S.R., S.R.B., M.A.-S., K.P., N.K., L.C.D.B., C.C., R.W., J.E.F., K.L.H.).ORCID 0000-0002-2420-4679
Mark C BlaserCardiovascular Division, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences (M.C.B., C.L.C., T.P., S.A.S., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0002-3923-9786
Majed Abdul-SamadToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada (S.R., S.R.B., M.A.-S., K.P., N.K., L.C.D.B., C.C., R.W., J.E.F., K.L.H.).ORCID 0009-0006-6007-3190
Kamalben PrajapatiToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada (S.R., S.R.B., M.A.-S., K.P., N.K., L.C.D.B., C.C., R.W., J.E.F., K.L.H.).
Negar KhosravianiToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada (S.R., S.R.B., M.A.-S., K.P., N.K., L.C.D.B., C.C., R.W., J.E.F., K.L.H.).
Tse Wing Winnie HoKeenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada (T.W.W.H., W.L.L.).ORCID 0000-0003-4465-7859
Leandro C D BredaToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada (S.R., S.R.B., M.A.-S., K.P., N.K., L.C.D.B., C.C., R.W., J.E.F., K.L.H.).
Crizza ChingToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada (S.R., S.R.B., M.A.-S., K.P., N.K., L.C.D.B., C.C., R.W., J.E.F., K.L.H.).
Natalie J GalantPrincess Margaret Cancer Center, Toronto, ON, Canada (N.J.G.).
Lindsey FiddesFaculty of Medicine (S.R., S.R.B., L.F., K.L.H.), University of Toronto, Toronto, ON, Canada.
Ruilin WuToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada (S.R., S.R.B., M.A.-S., K.P., N.K., L.C.D.B., C.C., R.W., J.E.F., K.L.H.).
Cassandra L CliftCardiovascular Division, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences (M.C.B., C.L.C., T.P., S.A.S., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0003-2441-4251
Tan PhamCardiovascular Division, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences (M.C.B., C.L.C., T.P., S.A.S., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Warren L LeeKeenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada (T.W.W.H., W.L.L.).ORCID 0000-0002-1788-6587
Sasha A SinghCardiovascular Division, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences (M.C.B., C.L.C., T.P., S.A.S., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0003-0929-3164
Elena AikawaCardiovascular Division, Department of Medicine, Center for Interdisciplinary Cardiovascular Sciences (M.C.B., C.L.C., T.P., S.A.S., E.A.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.ORCID 0000-0001-7835-2135
Jason E FishToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada (S.R., S.R.B., M.A.-S., K.P., N.K., L.C.D.B., C.C., R.W., J.E.F., K.L.H.).ORCID 0000-0003-0640-7277
Kathryn L HoweToronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada (S.R., S.R.B., M.A.-S., K.P., N.K., L.C.D.B., C.C., R.W., J.E.F., K.L.H.).ORCID 0000-0002-6519-2280
University Health Network · CABrigham and Women's Hospital · USSt. Michael's Hospital · CAPrincess Margaret Cancer Centre · CAUniversity of Toronto · 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

backgroundExtracellular vesicles (EVs) contain bioactive cargo including miRNAs and proteins that are released by cells during cell-cell communication. Endothelial cells (ECs) form the innermost lining of all blood vessels, interfacing with cells in the circulation and vascular wall. It is unknown whether ECs release EVs capable of governing recipient cells within these 2 separate compartments. Given their boundary location, we propose ECs use bidirectional release of distinct EV cargo in quiescent (healthy) and activated (atheroprone) states to communicate with cells within the circulation and blood vessel wall.

methodsEVs were isolated from primary human aortic ECs (plate and transwell grown; ±IL [interleukin]-1β activation), quantified, visualized, and analyzed by miRNA transcriptomics and proteomics. Apical and basolateral EC-EV release was determined by miRNA transfer, total internal reflection fluorescence and electron microscopy. Vascular reprogramming (RNA sequencing) and functional assays were performed on primary human monocytes or smooth muscle cells±EC-EVs.

resultsActivated ECs increased EV release, with miRNA and protein cargo related to atherosclerosis. EV-treated monocytes and smooth muscle cells revealed activated EC-EV altered pathways that were proinflammatory and atherogenic. ECs released more EVs apically, which increased with activation. Apical and basolateral EV cargo contained distinct transcriptomes and proteomes that were altered by EC activation. Notably, activated basolateral EC-EVs displayed greater changes in the EV secretome, with pathways specific to atherosclerosis. In silico analysis determined compartment-specific cargo released by the apical and basolateral surfaces of ECs can reprogram monocytes and smooth muscle cells, respectively, with functional assays and in vivo imaging supporting this concept.

conclusionsDemonstrating that ECs are capable of polarized EV cargo loading and directional EV secretion reveals a novel paradigm for endothelial communication, which may ultimately enhance the design of endothelial-based therapeutics for cardiovascular diseases such as atherosclerosis where ECs are persistently activated.

Indexed as

AtherosclerosisExtracellular VesiclesMicroRNAsCell CommunicationEndothelial CellsHumansMicroRNAsatherosclerosismicroRNAmonocytesmuscle, smoothproteomicsRNA-seq

Identifiers

PMID38174557
PMCPMC10826926
OpenAlexW4390586798

What OpenQuestion holds

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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.