Additionally, it has been shown that smooth muscle-specific acid ceramidase (Ac) gene knockout mice (Asah1fl/fl/SMCre) during hypercalcemia caused by high doses of vitamin D had more severe AMC in both the aorta and the coronary arteries as well as upregulation of osteopontin and RUNX2 (osteogenic markers) in the aortic and coronary arterial medial wall, and CD63, AnX2 (sEV markers) and ALP expression (mineralization marker) in the coronary arterial media in comparison with Asah1fl/fl/SMwt and WT/WT mice (57). This evidence concerns the gene SPP1 and hypercalcemia disease.