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Targeted Radiation Exposure Induces Accelerated Aortic Valve Remodeling in ApoE(−/−) Mice

Thoracic radiation therapy may result in accelerated atherosclerosis and in late aortic valve stenosis (AS). In this study, we assessed the feasibility of inducing radiation-induced AS using a targeted aortic valve irradiation (10 or 20 Grays) in two groups of C57Bl6/J (WT) and ApoE(−/−) mice compar...

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Autores principales: Rucher, Guillaume, Prigent, Kevin, Simard, Christophe, Frelin, Anne-Marie, Coquemont-Guyot, Maëlle, Elie, Nicolas, Delcroix, Nicolas, Perzo, Nicolas, Guinamard, Romain, Berger, Ludovic, Manrique, Alain
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531867/
https://www.ncbi.nlm.nih.gov/pubmed/37762794
http://dx.doi.org/10.3390/jcm12185854
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author Rucher, Guillaume
Prigent, Kevin
Simard, Christophe
Frelin, Anne-Marie
Coquemont-Guyot, Maëlle
Elie, Nicolas
Delcroix, Nicolas
Perzo, Nicolas
Guinamard, Romain
Berger, Ludovic
Manrique, Alain
author_facet Rucher, Guillaume
Prigent, Kevin
Simard, Christophe
Frelin, Anne-Marie
Coquemont-Guyot, Maëlle
Elie, Nicolas
Delcroix, Nicolas
Perzo, Nicolas
Guinamard, Romain
Berger, Ludovic
Manrique, Alain
author_sort Rucher, Guillaume
collection PubMed
description Thoracic radiation therapy may result in accelerated atherosclerosis and in late aortic valve stenosis (AS). In this study, we assessed the feasibility of inducing radiation-induced AS using a targeted aortic valve irradiation (10 or 20 Grays) in two groups of C57Bl6/J (WT) and ApoE(−/−) mice compared to a control (no irradiation). Peak aortic jet velocity was evaluated by echocardiography to characterize AS. T2*-weighted magnetic resonance imaging after injection of MPIO-αVCAM-1 was used to examine aortic inflammation resulting from irradiation. A T2* signal void on valve leaflets and aortic sinus was considered positive. Valve remodeling and mineralization were assessed using von Kossa staining. Finally, the impact of radiation on cell viability and cycle from aortic human valvular interstitial cells (hVICs) was also assessed. The targeted aortic valve irradiation in ApoE(−/−) mice resulted in an AS characterized by an increase in peak aortic jet velocity associated with valve leaflet and aortic sinus remodeling, including mineralization process, at the 3-month follow-up. There was a linear correlation between histological findings and peak aortic jet velocity (r = 0.57, p < 0.01). In addition, irradiation was associated with aortic root inflammation, evidenced by molecular MR imaging (p < 0.01). No significant effect of radiation exposure was detected on WT animals. Radiation exposure did not affect hVICs viability and cell cycle. We conclude that targeted radiation exposure of the aortic valve in mice results in ApoE(−/−), but not in WT, mice in an aortic valve remodeling mimicking the human lesions. This preclinical model could be a useful tool for future assessment of therapeutic interventions.
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spelling pubmed-105318672023-09-28 Targeted Radiation Exposure Induces Accelerated Aortic Valve Remodeling in ApoE(−/−) Mice Rucher, Guillaume Prigent, Kevin Simard, Christophe Frelin, Anne-Marie Coquemont-Guyot, Maëlle Elie, Nicolas Delcroix, Nicolas Perzo, Nicolas Guinamard, Romain Berger, Ludovic Manrique, Alain J Clin Med Article Thoracic radiation therapy may result in accelerated atherosclerosis and in late aortic valve stenosis (AS). In this study, we assessed the feasibility of inducing radiation-induced AS using a targeted aortic valve irradiation (10 or 20 Grays) in two groups of C57Bl6/J (WT) and ApoE(−/−) mice compared to a control (no irradiation). Peak aortic jet velocity was evaluated by echocardiography to characterize AS. T2*-weighted magnetic resonance imaging after injection of MPIO-αVCAM-1 was used to examine aortic inflammation resulting from irradiation. A T2* signal void on valve leaflets and aortic sinus was considered positive. Valve remodeling and mineralization were assessed using von Kossa staining. Finally, the impact of radiation on cell viability and cycle from aortic human valvular interstitial cells (hVICs) was also assessed. The targeted aortic valve irradiation in ApoE(−/−) mice resulted in an AS characterized by an increase in peak aortic jet velocity associated with valve leaflet and aortic sinus remodeling, including mineralization process, at the 3-month follow-up. There was a linear correlation between histological findings and peak aortic jet velocity (r = 0.57, p < 0.01). In addition, irradiation was associated with aortic root inflammation, evidenced by molecular MR imaging (p < 0.01). No significant effect of radiation exposure was detected on WT animals. Radiation exposure did not affect hVICs viability and cell cycle. We conclude that targeted radiation exposure of the aortic valve in mice results in ApoE(−/−), but not in WT, mice in an aortic valve remodeling mimicking the human lesions. This preclinical model could be a useful tool for future assessment of therapeutic interventions. MDPI 2023-09-08 /pmc/articles/PMC10531867/ /pubmed/37762794 http://dx.doi.org/10.3390/jcm12185854 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Rucher, Guillaume
Prigent, Kevin
Simard, Christophe
Frelin, Anne-Marie
Coquemont-Guyot, Maëlle
Elie, Nicolas
Delcroix, Nicolas
Perzo, Nicolas
Guinamard, Romain
Berger, Ludovic
Manrique, Alain
Targeted Radiation Exposure Induces Accelerated Aortic Valve Remodeling in ApoE(−/−) Mice
title Targeted Radiation Exposure Induces Accelerated Aortic Valve Remodeling in ApoE(−/−) Mice
title_full Targeted Radiation Exposure Induces Accelerated Aortic Valve Remodeling in ApoE(−/−) Mice
title_fullStr Targeted Radiation Exposure Induces Accelerated Aortic Valve Remodeling in ApoE(−/−) Mice
title_full_unstemmed Targeted Radiation Exposure Induces Accelerated Aortic Valve Remodeling in ApoE(−/−) Mice
title_short Targeted Radiation Exposure Induces Accelerated Aortic Valve Remodeling in ApoE(−/−) Mice
title_sort targeted radiation exposure induces accelerated aortic valve remodeling in apoe(−/−) mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531867/
https://www.ncbi.nlm.nih.gov/pubmed/37762794
http://dx.doi.org/10.3390/jcm12185854
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