Background: Though vascular calcification is a major risk factor for cardiovascular morbidity and mortality, the exact pathomechanism is to be elucidated. Histone deacetylases (HDACs), an epigenetic modulator that add acetyl group to lysine residues of histone tails, are implicated as a regulator in various pathological heart diseases. Here, we investigated the role of HDACs in vascular calcification. Methods and Results: Though they did not induce the calcification in normal growth medium, HDAC inhibitors of both non-selective and class I-selective HDAC inhibitors potentiated Phosphate-induced calcification as detected by von Kossa staining and quantification of calcium deposition in rat vascular smooth muscle cells (rVSMC). Pi-induced calcification reduced the HDAC1 protein but not mRNA levels. Downregulation of HDAC1 was blunted by treatment with proteasome inhibitors. HDAC1 poly-ubiquitination was induced by phosphate-treatment on VSMC as determined by immunoprecipitation with ubiquitin antibody. Conclusions: These results suggest that phosphate induces HDAC1 protein degradation and then results in vascular calcification which would be an important mechanism for induction of vascular calcification.