RUNX2 and hypercalcemia disease: We first revealed that Ac gene deletion in SMCs using Asah1fl/fl/SMCre mice greatly increased the calcification in aortic and coronary arterial medial wall in comparison to their littermates during hypercalcemia caused by high doses of Vit D. In addition, “bone” transcription factors (e.g., RUNX2) and matrix proteins (e.g. osteopontin) have been noticeably increased in the aortic and coronary arterial medial wall of Asah1fl/fl/SMCre mice treated with Vit D compared to their littermates (Asah1fl/fl/SMwt and WT/WT).