Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery

Costanza Emanueli; Andrew I U Shearn; Abas Laftah; Francesca Fiorentino; Barnaby C Reeves; Cristina Beltrami; Andrew Mumford; Aled Clayton; Mark Gurney; Saran Shantikumar; Gianni D Angelini

doi:10.1371/journal.pone.0154274

Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery

Costanza Emanueli, Andrew I U Shearn, Abas Laftah, Francesca Fiorentino, Barnaby C Reeves, Cristina Beltrami, Andrew Mumford, Aled Clayton, Mark Gurney, Saran Shantikumar, Gianni D Angelini

Research output: Contribution to journal › Article (Academic Journal) › peer-review

110 Citations (Scopus)

430 Downloads (Pure)

Abstract

INTRODUCTION: Exosome nanoparticles carry a composite cargo, including microRNAs (miRs). Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG) surgery, we investigated if: 1) exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2) circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn), the current "gold standard" surrogate biomarker of myocardial damage.

METHODS AND RESULTS: The concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210), non-cardiovascular (miR-122) and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs.

CONCLUSIONS: The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients.

Original language	English
Article number	e0154274
Number of pages	21
Journal	PLoS ONE
Volume	11
Issue number	4
DOIs	https://doi.org/10.1371/journal.pone.0154274
Publication status	Published - 29 Apr 2016

Research Groups and Themes

BTC (Bristol Trials Centre)
Centre for Surgical Research

Access to Document

10.1371/journal.pone.0154274

journal.pone.0154274
This is the final published version of the article (version of record). It first appeared online via Public Library of Science at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0154274. Please refer to any applicable terms of use of the publisher.
Final published version, 4.82 MBLicence: CC BY

Handle.net

Persistent link

Fingerprint

Dive into the research topics of 'Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery'. Together they form a unique fingerprint.

Resubmmission of MicroRNAs in ischaemic heart disease and diabetes mellitus: from cardiac surgery to basic science - and back
Carmichael, A. J. (Principal Investigator)
1/06/15 → 31/05/20
Project: Research
NIHR Biomedical Research Unit - Cardiovascular Disease
Antognozzi, M. (Principal Investigator)
1/04/12 → 31/03/17
Project: Research, Parent

Professor Gianni D Angelini
- G.D.Angelinibristol.acuk
- Bristol Medical School (THS) - BHF Professor of Cardiac Surgery and Director
- Bristol Population Health Science Institute
Person: Academic , Member

Cite this

Emanueli, C., Shearn, A. I. U., Laftah, A., Fiorentino, F., Reeves, B. C., Beltrami, C., Mumford, A., Clayton, A., Gurney, M., Shantikumar, S., & Angelini, G. D. (2016). Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery. PLoS ONE, 11(4), Article e0154274. https://doi.org/10.1371/journal.pone.0154274

@article{752a6183a0b64122b3f6e50c4fd22be5,

title = "Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery",

abstract = "INTRODUCTION: Exosome nanoparticles carry a composite cargo, including microRNAs (miRs). Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG) surgery, we investigated if: 1) exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2) circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn), the current {"}gold standard{"} surrogate biomarker of myocardial damage.METHODS AND RESULTS: The concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210), non-cardiovascular (miR-122) and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs.CONCLUSIONS: The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients.",

author = "Costanza Emanueli and Shearn, {Andrew I U} and Abas Laftah and Francesca Fiorentino and Reeves, {Barnaby C} and Cristina Beltrami and Andrew Mumford and Aled Clayton and Mark Gurney and Saran Shantikumar and Angelini, {Gianni D}",

year = "2016",

month = apr,

day = "29",

doi = "10.1371/journal.pone.0154274",

language = "English",

volume = "11",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "4",

}

Emanueli, C, Shearn, AIU, Laftah, A, Fiorentino, F, Reeves, BC, Beltrami, C, Mumford, A, Clayton, A, Gurney, M, Shantikumar, S & Angelini, GD 2016, 'Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery', PLoS ONE, vol. 11, no. 4, e0154274. https://doi.org/10.1371/journal.pone.0154274

Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery. / Emanueli, Costanza; Shearn, Andrew I U; Laftah, Abas et al.
In: PLoS ONE, Vol. 11, No. 4, e0154274, 29.04.2016.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs

T2 - An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery

AU - Emanueli, Costanza

AU - Shearn, Andrew I U

AU - Laftah, Abas

AU - Fiorentino, Francesca

AU - Reeves, Barnaby C

AU - Beltrami, Cristina

AU - Mumford, Andrew

AU - Clayton, Aled

AU - Gurney, Mark

AU - Shantikumar, Saran

AU - Angelini, Gianni D

PY - 2016/4/29

Y1 - 2016/4/29

N2 - INTRODUCTION: Exosome nanoparticles carry a composite cargo, including microRNAs (miRs). Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG) surgery, we investigated if: 1) exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2) circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn), the current "gold standard" surrogate biomarker of myocardial damage.METHODS AND RESULTS: The concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210), non-cardiovascular (miR-122) and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs.CONCLUSIONS: The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients.

AB - INTRODUCTION: Exosome nanoparticles carry a composite cargo, including microRNAs (miRs). Cultured cardiovascular cells release miR-containing exosomes. The exosomal trafficking of miRNAs from the heart is largely unexplored. Working on clinical samples from coronary-artery by-pass graft (CABG) surgery, we investigated if: 1) exosomes containing cardiac miRs and hence putatively released by cardiac cells increase in the circulation after surgery; 2) circulating exosomes and exosomal cardiac miRs correlate with cardiac troponin (cTn), the current "gold standard" surrogate biomarker of myocardial damage.METHODS AND RESULTS: The concentration of exosome-sized nanoparticles was determined in serial plasma samples. Cardiac-expressed (miR-1, miR-24, miR-133a/b, miR-208a/b, miR-210), non-cardiovascular (miR-122) and quality control miRs were measured in whole plasma and in plasma exosomes. Linear regression analyses were employed to establish the extent to which the circulating individual miRs, exosomes and exosomal cardiac miR correlated with cTn-I. Cardiac-expressed miRs and the nanoparticle number increased in the plasma on completion of surgery for up to 48 hours. The exosomal concentration of cardiac miRs also increased after CABG. Cardiac miRs in the whole plasma did not correlate significantly with cTn-I. By contrast cTn-I was positively correlated with the plasma exosome level and the exosomal cardiac miRs.CONCLUSIONS: The plasma concentrations of exosomes and their cargo of cardiac miRs increased in patients undergoing CABG and were positively correlated with hs-cTnI. These data provide evidence that CABG induces the trafficking of exosomes from the heart to the peripheral circulation. Future studies are necessary to investigate the potential of circulating exosomes as clinical biomarkers in cardiac patients.

U2 - 10.1371/journal.pone.0154274

DO - 10.1371/journal.pone.0154274

M3 - Article (Academic Journal)

C2 - 27128471

SN - 1932-6203

VL - 11

JO - PLoS ONE

JF - PLoS ONE

IS - 4

M1 - e0154274

ER -

Emanueli C, Shearn AIU, Laftah A, Fiorentino F, Reeves BC, Beltrami C et al. Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery. PLoS ONE. 2016 Apr 29;11(4):e0154274. doi: 10.1371/journal.pone.0154274

Coronary Artery-Bypass-Graft Surgery Increases the Plasma Concentration of Exosomes Carrying a Cargo of Cardiac MicroRNAs: An Example of Exosome Trafficking Out of the Human Heart with Potential for Cardiac Biomarker Discovery

Abstract

Research Groups and Themes

Access to Document

Handle.net

Fingerprint

Projects

Resubmmission of MicroRNAs in ischaemic heart disease and diabetes mellitus: from cardiac surgery to basic science - and back

NIHR Biomedical Research Unit - Cardiovascular Disease

Profiles

Professor Gianni D Angelini

Cite this