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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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 |
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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 |
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