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Master Thesis

Evaluation of a preventive therapy in a model of calcified aortic stenosis

Abstract : Introduction: Mediastinal radiotherapy is a major cause of cardiac complications including aortic stenosis (AS). However, there is a lack of a preclinical model of AS mimicking radiation-induced lesions. In addition, AS is the most frequent valvular disease. In inoperable patients without effective medical treatment, the prognosis is poor. This project consists in evaluating by Imaging and Histology, the effectiveness of a preventive therapy in a mouse model of AS. Materials and methods: Targeted irradiation of the aortic valve (10 or 20Gy) in C57/Bl6/J (WT) and ApoE - /- mice was carried out to develop an AS model. Once the model had been developed, inorganic pyrophosphate (PPi) was studied as a preventive therapy in ApoE -/- (0 or 10Gy) mice. The assessment tools were echocardiography and cardiac magnetic resonance imaging. Cardiac and valve remodeling was studied in Histology using von Kossa and Rouge Picro-Sirius stains. Results: Targeted irradiation in ApoE -/- mice demonstrated the development of AS. This AS was characterized by increased velocities, trans valvular gradients and increased mineralization in von Kossa. The PPi made it possible to completely cancel the observed effects of radiotherapy and to demonstrate the reproducibility of the model in untreated ApoE -/- mice. Conclusion: Targeted irradiation on the aortic valve allowed the development of an AS in ApoE -/- mice. Based on Imaging and Histology, PPi appears to be an effective treatment in this model.
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Submitted on : Thursday, March 4, 2021 - 12:36:47 PM
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Kevin Prigent. Evaluation of a preventive therapy in a model of calcified aortic stenosis. Human health and pathology. 2020. ⟨dumas-03159151⟩



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