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

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Τίτλος: Targeted Radiation Exposure Induces Accelerated Aortic Valve Remodeling in ApoE−/− Mice
Συγγραφείς: Rucher, Guillaume, Prigent, Kevin, Simard, Christophe, Frelin, Anne-Marie, Coquemont-Guyot, Maëlle, Elie, Nicolas, Delcroix, Nicolas, Perzo, Nicolas, Guinamard, Romain, Berger, Ludovic, Manrique, Alain
Συνεισφορές: Grand Accélérateur National d'Ions Lourds (GANIL), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), ANR-10-EQPX-0014,REC-HADRON,RECherche fondamentale en HADRONthérapie(2010), ANR-16-RHUS-0003,STOP-AS,STOP-AS(2016)
Πηγή: Journal of Clinical Medicine ; https://hal.science/hal-04246506 ; Journal of Clinical Medicine, 2023, 12 (18), pp.5854. ⟨10.3390/jcm12185854⟩
Στοιχεία εκδότη: CCSD
Έτος έκδοσης: 2023
Θεματικοί όροι: [PHYS]Physics [physics]
Περιγραφή: International audience ; 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.
Τύπος εγγράφου: article in journal/newspaper
Γλώσσα: English
Relation: INSPIRE: 2711679
DOI: 10.3390/jcm12185854
Διαθεσιμότητα: https://hal.science/hal-04246506
https://doi.org/10.3390/jcm12185854
Αριθμός Καταχώρησης: edsbas.744778F2
Βάση Δεδομένων: BASE
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  Data: Targeted Radiation Exposure Induces Accelerated Aortic Valve Remodeling in ApoE−/− Mice
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  Data: Journal of Clinical Medicine ; https://hal.science/hal-04246506 ; Journal of Clinical Medicine, 2023, 12 (18), pp.5854. ⟨10.3390/jcm12185854⟩
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  Data: International audience ; &lt;jats:p&gt;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 &lt; 0.01). In addition, irradiation was associated with aortic root inflammation, evidenced by molecular MR imaging (p &lt; 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.&lt;/jats:p&gt;
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