Effect of a high fat diet and vitamin D3 supplementation in the aortic valvulopathy EgfrWa2/Wa2 murin model

Abstract

The pathophysiology of aortic stenosis (AS), the most common acquired valvulopathy, is not fully understood and there is to date no treatment to slow or stop the progression of the disease. To define new therapeutic strategies, reproductible and adequate animal models of AS remain essentials and is lacking. A new mouse model has been proposed consisting of a single-nucleotide homozygous substitution mutation in the gene encoding EGFr, known as C57BL6 EgfrWa2/Wa2. However, it has been recently shown that aortic regurgitation (AR) remained prevalent, and that AS was rare or absent. The aim of this study was to evaluate the effect of a high fat diet (HFD) and vitamin D3 supplementation in this model. C57BL6 EgfrWa2/Wa2 mice were fed with HFD and were subcutaneous injected with vitamin D3 (16 UI/kg UI, 3 times a week, n = 16) during eighteen weeks. We used as control C57BL6 EgfrWa2/Wa2 mice fed without HFD and vitamin D3 (n = 12). Echocardiography was performed 3 and 6 months later. Blood serum 25(OH)2D3, 1,25(OH)2D3, calcium, total cholesterol, phosphates and creatinine were analyzed, and histology/IHC were performed at 6 months to assess valvular fibrosis, calcification and inflammation. Echocardiographic analysis did not show any improvement of the model with HFD and vitamin D3 supplementation. We observed pure severe AS in only two animals in each group and predominant AR in remaining animals. The different variables studied by echocardiography are represented in Table 1. Vitamin D3 supplementation and HFD did not affect inflammation and calcification, although total cholesterol level was increased. These results suggest that HFD and vitamin D3 supplementation had no effect on the C57BL6 EgfrWa2/Wa2 mice model. This model essentially mimics AR and no AS. Further studies are needed to find a reliable animal model of AS.