Evidence map›Paper›PMID 25995315›Full record

ArticleCirculation2015

Circulating Exosomes Induced by Cardiac Pressure Overload Contain Functional Angiotensin II Type 1 Receptors.

Gianluigi Pironti, Ryan T Strachan, Dennis Abraham, Samuel Mon-Wei Yu, Minyong Chen, Wei Chen, Kenji Hanada, Lan Mao, Lewis J Watson, Howard A Rockman

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

Article in Circulation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
161citing papers in PubMed, 4 pooled it
9.8field-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

161 citing papers in PubMed, 4 syntheses or guidelines pooled it, 226 citations in OpenAlex.

  1. Pooled it
  2. Extracellular vesicles and their effect on vascular haemodynamics: a systematic review.Hypertension research : official journal of the Japanese Society of Hypertension · 2024
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101 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Gianluigi PirontiFrom Departments of Medicine (G.P., R.T.S., D.A., S.M.-W.Y., M.C., W.C., K.H., L.M., L.J.W., H.A.R.), Cell Biology (H.A.R.), and Molecular Genetics and Microbiology (H.A.R.), Duke University Medical Center, Durham, NC.
Ryan T StrachanFrom Departments of Medicine (G.P., R.T.S., D.A., S.M.-W.Y., M.C., W.C., K.H., L.M., L.J.W., H.A.R.), Cell Biology (H.A.R.), and Molecular Genetics and Microbiology (H.A.R.), Duke University Medical Center, Durham, NC.
Dennis AbrahamFrom Departments of Medicine (G.P., R.T.S., D.A., S.M.-W.Y., M.C., W.C., K.H., L.M., L.J.W., H.A.R.), Cell Biology (H.A.R.), and Molecular Genetics and Microbiology (H.A.R.), Duke University Medical Center, Durham, NC.
Samuel Mon-Wei YuFrom Departments of Medicine (G.P., R.T.S., D.A., S.M.-W.Y., M.C., W.C., K.H., L.M., L.J.W., H.A.R.), Cell Biology (H.A.R.), and Molecular Genetics and Microbiology (H.A.R.), Duke University Medical Center, Durham, NC.
Minyong ChenFrom Departments of Medicine (G.P., R.T.S., D.A., S.M.-W.Y., M.C., W.C., K.H., L.M., L.J.W., H.A.R.), Cell Biology (H.A.R.), and Molecular Genetics and Microbiology (H.A.R.), Duke University Medical Center, Durham, NC.
Wei ChenFrom Departments of Medicine (G.P., R.T.S., D.A., S.M.-W.Y., M.C., W.C., K.H., L.M., L.J.W., H.A.R.), Cell Biology (H.A.R.), and Molecular Genetics and Microbiology (H.A.R.), Duke University Medical Center, Durham, NC.
Kenji HanadaFrom Departments of Medicine (G.P., R.T.S., D.A., S.M.-W.Y., M.C., W.C., K.H., L.M., L.J.W., H.A.R.), Cell Biology (H.A.R.), and Molecular Genetics and Microbiology (H.A.R.), Duke University Medical Center, Durham, NC.
Lan MaoFrom Departments of Medicine (G.P., R.T.S., D.A., S.M.-W.Y., M.C., W.C., K.H., L.M., L.J.W., H.A.R.), Cell Biology (H.A.R.), and Molecular Genetics and Microbiology (H.A.R.), Duke University Medical Center, Durham, NC.
Lewis J WatsonFrom Departments of Medicine (G.P., R.T.S., D.A., S.M.-W.Y., M.C., W.C., K.H., L.M., L.J.W., H.A.R.), Cell Biology (H.A.R.), and Molecular Genetics and Microbiology (H.A.R.), Duke University Medical Center, Durham, NC.
Howard A RockmanFrom Departments of Medicine (G.P., R.T.S., D.A., S.M.-W.Y., M.C., W.C., K.H., L.M., L.J.W., H.A.R.), Cell Biology (H.A.R.), and Molecular Genetics and Microbiology (H.A.R.), Duke University Medical Center, Durham, NC. h.rockman@duke.edu.
Duke University · US

Funding

Regulation of Beta-Adrenergic Receptor Signaling by S-NitrosylationP01HL075443 · NHLBI · DUKE UNIVERSITY · PI ROCKMAN, HOWARD A · 2004 to 2019
$26.1M
MECHANISMS OF MALADAPTATION IN HEART FAILURER01HL056687 · NHLBI · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI Howard A Rockman · 1996 to 2026
$12.3M
MULTIDISCIPLINARY HEART &VASCULAR DISEASEST32HL007101 · NHLBI · DUKE UNIVERSITY · PI FREEDMAN, NEIL J. · 1985 to 2020
$9.8M
Clinical Oncology Research Career Development ProgramK12CA100639 · NCI · DUKE UNIVERSITY · PI LYERLY, HERBERT KIM · 2004 to 2013
$8.0M
Renal Genomics CoreP30DK096493 · NIDDK · DUKE UNIVERSITY · PI PATEL, UPTAL D · 2012 to 2016
$5.9M
Inhibition of Wnt/B-Catenin Signaling in Colorectal Cancer TherapyR01CA172570 · NCI · DUKE UNIVERSITY · PI CHEN, WEI · 2013 to 2017
$1.6M
TREK-1 in fibroblast differentiation and cardiac fibrosis developmentK08HL125905 · NHLBI · DUKE UNIVERSITY · PI ABRAHAM, DENNIS · 2015 to 2019
$746k
NCI NIH HHS K12 CA100639NCI NIH HHS R01 CA172570NHLBI NIH HHS K08 HL125905NHLBI NIH HHS P01 HL075443NHLBI NIH HHS R01 HL056687NHLBI NIH HHS T32 HL007101NIDDK NIH HHS P30 DK096493
6 · The paper itself

Abstract

backgroundWhether biomechanical force on the heart can induce exosome secretion to modulate cardiovascular function is not known. We investigated the secretion and activity of exosomes containing a key receptor in cardiovascular function, the angiotensin II type I receptor (AT1R). METHODS AND

resultsExosomes containing AT1Rs were isolated from the media overlying AT1R-overexpressing cells exposed to osmotic stretch and from sera of mice undergoing cardiac pressure overload. The presence of AT1Rs in exosomes was confirmed by both electron microscopy and radioligand receptor binding assays and shown to require β-arrestin2, a multifunctional adaptor protein essential for receptor trafficking. We show that functional AT1Rs are transferred via exosomes in an in vitro model of cellular stretch. Using mice with global and cardiomyocyte conditional deletion of β-arrestin2, we show that under conditions of in vivo pressure overload the cellular source of the exocytosis of exosomes containing AT1R is the cardiomyocyte. Exogenously administered AT1R-enriched exosomes target cardiomyocytes, skeletal myocytes, and mesenteric resistance vessels and are sufficient to confer blood pressure responsiveness to angiotensin II infusion in AT1R knockout mice.

conclusionsAT1R-enriched exosomes are released from the heart under conditions of in vivo cellular stress to likely modulate vascular responses to neurohormonal stimulation. In the context of the whole organism, the concept of G protein-coupled receptor trafficking should consider circulating exosomes as part of the reservoir of functional AT1Rs.

Indexed as

Stress, MechanicalAnimalsArrestinsbeta-ArrestinsBlood PressureConstrictionExosomesFemaleHEK293 CellsHumansMaleMiceMice, Inbred C57BLMice, KnockoutMicroscopy, ElectronMuscle CellsArrestinsbeta-ArrestinsReceptor, Angiotensin, Type 1RNA, Small Interferingbeta-arrestinexosomeshypertensionreceptors, angiotensinsignal transduction

Identifiers

PMID25995315
PMCPMC4470842
OpenAlexW2099039944

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.