Cargando…

Late plasma exosome microRNA-21-5p depicts magnitude of reverse ventricular remodeling after early surgical repair of primary mitral valve regurgitation

INTRODUCTION: Primary mitral valve regurgitation (MR) results from degeneration of mitral valve apparatus. Mechanisms leading to incomplete postoperative left ventricular (LV) reverse remodeling (Rev–Rem) despite timely and successful surgical mitral valve repair (MVR) remain unknown. Plasma exosome...

Descripción completa

Detalles Bibliográficos
Autores principales: Pizzino, Fausto, Furini, Giulia, Casieri, Valentina, Mariani, Massimiliano, Bianchi, Giacomo, Storti, Simona, Chiappino, Dante, Maffei, Stefano, Solinas, Marco, Aquaro, Giovanni Donato, Lionetti, Vincenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9373041/
https://www.ncbi.nlm.nih.gov/pubmed/35966562
http://dx.doi.org/10.3389/fcvm.2022.943068
_version_ 1784767516570025984
author Pizzino, Fausto
Furini, Giulia
Casieri, Valentina
Mariani, Massimiliano
Bianchi, Giacomo
Storti, Simona
Chiappino, Dante
Maffei, Stefano
Solinas, Marco
Aquaro, Giovanni Donato
Lionetti, Vincenzo
author_facet Pizzino, Fausto
Furini, Giulia
Casieri, Valentina
Mariani, Massimiliano
Bianchi, Giacomo
Storti, Simona
Chiappino, Dante
Maffei, Stefano
Solinas, Marco
Aquaro, Giovanni Donato
Lionetti, Vincenzo
author_sort Pizzino, Fausto
collection PubMed
description INTRODUCTION: Primary mitral valve regurgitation (MR) results from degeneration of mitral valve apparatus. Mechanisms leading to incomplete postoperative left ventricular (LV) reverse remodeling (Rev–Rem) despite timely and successful surgical mitral valve repair (MVR) remain unknown. Plasma exosomes (pEXOs) are smallest nanovesicles exerting early postoperative cardioprotection. We hypothesized that late plasma exosomal microRNAs (miRs) contribute to Rev–Rem during the late postoperative period. METHODS: Primary MR patients (n = 19; age, 45–71 years) underwent cardiac magnetic resonance imaging and blood sampling before (T0) and 6 months after (T1) MVR. The postoperative LV Rev–Rem was assessed in terms of a decrease in LV end-diastolic volume and patients were stratified into high (HiR-REM) and low (LoR-REM) LV Rev–Rem subgroups. Isolated pEXOs were quantified by nanoparticle tracking analysis. Exosomal microRNA (miR)-1, –21–5p, –133a, and –208a levels were measured by RT-qPCR. Anti-hypertrophic effects of pEXOs were tested in HL-1 cardiomyocytes cultured with angiotensin II (AngII, 1 μM for 48 h). RESULTS: Surgery zeroed out volume regurgitation in all patients. Although preoperative pEXOs were similar in both groups, pEXO levels increased after MVR in HiR-REM patients (+0.75-fold, p = 0.016), who showed lower cardiac mass index (–11%, p = 0.032). Postoperative exosomal miR-21-5p values of HiR-REM patients were higher than other groups (p < 0.05). In vitro, T1-pEXOs isolated from LoR-REM patients boosted the AngII-induced cardiomyocyte hypertrophy, but not postoperative exosomes of HiR-REM. This adaptive effect was counteracted by miR-21-5p inhibition. SUMMARY/CONCLUSION: High levels of miR-21-5p-enriched pEXOs during the late postoperative period depict higher LV Rev–Rem after MVR. miR-21-5p-enriched pEXOs may be helpful to predict and to treat incomplete LV Rev–Rem after successful early surgical MVR.
format Online
Article
Text
id pubmed-9373041
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-93730412022-08-13 Late plasma exosome microRNA-21-5p depicts magnitude of reverse ventricular remodeling after early surgical repair of primary mitral valve regurgitation Pizzino, Fausto Furini, Giulia Casieri, Valentina Mariani, Massimiliano Bianchi, Giacomo Storti, Simona Chiappino, Dante Maffei, Stefano Solinas, Marco Aquaro, Giovanni Donato Lionetti, Vincenzo Front Cardiovasc Med Cardiovascular Medicine INTRODUCTION: Primary mitral valve regurgitation (MR) results from degeneration of mitral valve apparatus. Mechanisms leading to incomplete postoperative left ventricular (LV) reverse remodeling (Rev–Rem) despite timely and successful surgical mitral valve repair (MVR) remain unknown. Plasma exosomes (pEXOs) are smallest nanovesicles exerting early postoperative cardioprotection. We hypothesized that late plasma exosomal microRNAs (miRs) contribute to Rev–Rem during the late postoperative period. METHODS: Primary MR patients (n = 19; age, 45–71 years) underwent cardiac magnetic resonance imaging and blood sampling before (T0) and 6 months after (T1) MVR. The postoperative LV Rev–Rem was assessed in terms of a decrease in LV end-diastolic volume and patients were stratified into high (HiR-REM) and low (LoR-REM) LV Rev–Rem subgroups. Isolated pEXOs were quantified by nanoparticle tracking analysis. Exosomal microRNA (miR)-1, –21–5p, –133a, and –208a levels were measured by RT-qPCR. Anti-hypertrophic effects of pEXOs were tested in HL-1 cardiomyocytes cultured with angiotensin II (AngII, 1 μM for 48 h). RESULTS: Surgery zeroed out volume regurgitation in all patients. Although preoperative pEXOs were similar in both groups, pEXO levels increased after MVR in HiR-REM patients (+0.75-fold, p = 0.016), who showed lower cardiac mass index (–11%, p = 0.032). Postoperative exosomal miR-21-5p values of HiR-REM patients were higher than other groups (p < 0.05). In vitro, T1-pEXOs isolated from LoR-REM patients boosted the AngII-induced cardiomyocyte hypertrophy, but not postoperative exosomes of HiR-REM. This adaptive effect was counteracted by miR-21-5p inhibition. SUMMARY/CONCLUSION: High levels of miR-21-5p-enriched pEXOs during the late postoperative period depict higher LV Rev–Rem after MVR. miR-21-5p-enriched pEXOs may be helpful to predict and to treat incomplete LV Rev–Rem after successful early surgical MVR. Frontiers Media S.A. 2022-07-29 /pmc/articles/PMC9373041/ /pubmed/35966562 http://dx.doi.org/10.3389/fcvm.2022.943068 Text en Copyright © 2022 Pizzino, Furini, Casieri, Mariani, Bianchi, Storti, Chiappino, Maffei, Solinas, Aquaro and Lionetti. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Pizzino, Fausto
Furini, Giulia
Casieri, Valentina
Mariani, Massimiliano
Bianchi, Giacomo
Storti, Simona
Chiappino, Dante
Maffei, Stefano
Solinas, Marco
Aquaro, Giovanni Donato
Lionetti, Vincenzo
Late plasma exosome microRNA-21-5p depicts magnitude of reverse ventricular remodeling after early surgical repair of primary mitral valve regurgitation
title Late plasma exosome microRNA-21-5p depicts magnitude of reverse ventricular remodeling after early surgical repair of primary mitral valve regurgitation
title_full Late plasma exosome microRNA-21-5p depicts magnitude of reverse ventricular remodeling after early surgical repair of primary mitral valve regurgitation
title_fullStr Late plasma exosome microRNA-21-5p depicts magnitude of reverse ventricular remodeling after early surgical repair of primary mitral valve regurgitation
title_full_unstemmed Late plasma exosome microRNA-21-5p depicts magnitude of reverse ventricular remodeling after early surgical repair of primary mitral valve regurgitation
title_short Late plasma exosome microRNA-21-5p depicts magnitude of reverse ventricular remodeling after early surgical repair of primary mitral valve regurgitation
title_sort late plasma exosome microrna-21-5p depicts magnitude of reverse ventricular remodeling after early surgical repair of primary mitral valve regurgitation
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9373041/
https://www.ncbi.nlm.nih.gov/pubmed/35966562
http://dx.doi.org/10.3389/fcvm.2022.943068
work_keys_str_mv AT pizzinofausto lateplasmaexosomemicrorna215pdepictsmagnitudeofreverseventricularremodelingafterearlysurgicalrepairofprimarymitralvalveregurgitation
AT furinigiulia lateplasmaexosomemicrorna215pdepictsmagnitudeofreverseventricularremodelingafterearlysurgicalrepairofprimarymitralvalveregurgitation
AT casierivalentina lateplasmaexosomemicrorna215pdepictsmagnitudeofreverseventricularremodelingafterearlysurgicalrepairofprimarymitralvalveregurgitation
AT marianimassimiliano lateplasmaexosomemicrorna215pdepictsmagnitudeofreverseventricularremodelingafterearlysurgicalrepairofprimarymitralvalveregurgitation
AT bianchigiacomo lateplasmaexosomemicrorna215pdepictsmagnitudeofreverseventricularremodelingafterearlysurgicalrepairofprimarymitralvalveregurgitation
AT stortisimona lateplasmaexosomemicrorna215pdepictsmagnitudeofreverseventricularremodelingafterearlysurgicalrepairofprimarymitralvalveregurgitation
AT chiappinodante lateplasmaexosomemicrorna215pdepictsmagnitudeofreverseventricularremodelingafterearlysurgicalrepairofprimarymitralvalveregurgitation
AT maffeistefano lateplasmaexosomemicrorna215pdepictsmagnitudeofreverseventricularremodelingafterearlysurgicalrepairofprimarymitralvalveregurgitation
AT solinasmarco lateplasmaexosomemicrorna215pdepictsmagnitudeofreverseventricularremodelingafterearlysurgicalrepairofprimarymitralvalveregurgitation
AT aquarogiovannidonato lateplasmaexosomemicrorna215pdepictsmagnitudeofreverseventricularremodelingafterearlysurgicalrepairofprimarymitralvalveregurgitation
AT lionettivincenzo lateplasmaexosomemicrorna215pdepictsmagnitudeofreverseventricularremodelingafterearlysurgicalrepairofprimarymitralvalveregurgitation