Ablation of the Sost gene prevents hallmarks of calcific aortic valve disease in a high-cholesterol mouse model

The purpose of this study was to understand the effect of sclerostin genetic ablation (gene: Sost) on aortic valve fibrocalcification in an aged, high-cholesterol diet mouse model. Sclerostin is a potent agent in bone remodeling. It both blocks Wnt-mediated osteoblast bone deposition and spurs RANKL-mediated osteoclast maturation and subsequent bone resorption. A monoclonal antibody was recently approved as a treatment for post-menopausal osteoporosis but clinical trials indicated potential cardiovascular side effects. This study aimed to begin to understand the potential role of sclerostin in the aortic valve. C57BL6/J background mice with wild-type or double knockout of the Sost gene were aged to 4 months on standard chow and then transferred to high-cholesterol diet for 8 months. Aortic roots were harvested at one-year of age. N=3 aortic roots from each experimental group were used for this RNA sequencing analysis.