Objective: The use of animal models of aortic stenosis(AS) remains essential to further elucidate its pathophysiology and to evaluate new therapeutic strategies. The waved-2 mouse AS model has been proposed;data have ...Objective: The use of animal models of aortic stenosis(AS) remains essential to further elucidate its pathophysiology and to evaluate new therapeutic strategies. The waved-2 mouse AS model has been proposed;data have indicated that while aortic regurgitation(AR) is effectively induced, development of AS is rare.We aimed to evaluate the effect of high-fat diet(HFD) and vitamin D_3 supplementation in this model.Methods: HFD and subcutaneous vitamin D_3 injections were initiated at the age of 6 weeks until the age of 6(n = 16, 6-month treatment group) and 9(n = 11, 9-month treatment group) months. Twelve waved-2 mice without supplementation were used as control. Echocardiography was performed at 3, 6 and 9 months. Blood serum analysis(calcium, 1,25(OH)_2D_3 and cholesterol), histology and immunohistochemistry(CD-31, CD-68 and osteopontin) were evaluated at the end of the experiment(6 or 9 months).Results: Total cholesterol and 1,25(OH)_2D_3 were significantly increased relative to the control group. HFD and vitamin D_3 supplementation did result in improvements to the model, since AS was only detected in 6(15.3%) mice(2 in the 3 groups) and AR was developed in the remaining animals. Echocardiographic parameters, fibrosis, thickness, inflammation and valvular calcification, were not significantly different between the 6-month treatment and control groups. Similar results were also observed in the 9-month treatment group.Conclusion: These results suggest that HFD and vitamin D_3 supplementation have no effect in the waved-2 mouse model. This model essentially mimics AR and rarely AS. Further studies are needed to find a reliable animal model of AS.展开更多
基金supported by the French Government,managed by the National Research Agency(ANR)under the program‘‘Investissements d’avenir" with the reference ANR-16-RHUS-0003(RHU project ‘‘Search Treatment and Improve Outcome of Patients with Aortic Stenosis"(STOP-AS)-Hélène Eltchaninoff)Bérénice Colleville’s doctoral program was funded by the Fédération Hospitalo-Universitaire ‘‘Early markers of cardiovascular REMODeling in Valvulopathy and Heart Failure"(REMOD-VHF)and the Rouen Normandy University
文摘Objective: The use of animal models of aortic stenosis(AS) remains essential to further elucidate its pathophysiology and to evaluate new therapeutic strategies. The waved-2 mouse AS model has been proposed;data have indicated that while aortic regurgitation(AR) is effectively induced, development of AS is rare.We aimed to evaluate the effect of high-fat diet(HFD) and vitamin D_3 supplementation in this model.Methods: HFD and subcutaneous vitamin D_3 injections were initiated at the age of 6 weeks until the age of 6(n = 16, 6-month treatment group) and 9(n = 11, 9-month treatment group) months. Twelve waved-2 mice without supplementation were used as control. Echocardiography was performed at 3, 6 and 9 months. Blood serum analysis(calcium, 1,25(OH)_2D_3 and cholesterol), histology and immunohistochemistry(CD-31, CD-68 and osteopontin) were evaluated at the end of the experiment(6 or 9 months).Results: Total cholesterol and 1,25(OH)_2D_3 were significantly increased relative to the control group. HFD and vitamin D_3 supplementation did result in improvements to the model, since AS was only detected in 6(15.3%) mice(2 in the 3 groups) and AR was developed in the remaining animals. Echocardiographic parameters, fibrosis, thickness, inflammation and valvular calcification, were not significantly different between the 6-month treatment and control groups. Similar results were also observed in the 9-month treatment group.Conclusion: These results suggest that HFD and vitamin D_3 supplementation have no effect in the waved-2 mouse model. This model essentially mimics AR and rarely AS. Further studies are needed to find a reliable animal model of AS.
