Targets ATF3 to Reduce Calcium Deposition in Vascular Smooth Muscle Cells.

Vascular calcification, the ectopic deposition of calcium in blood vessels, develops in association with various metabolic diseases and atherosclerosis and is an independent predictor of morbidity and mortality associated with these diseases. Herein, we report that reduction of () causes an increase in activating transcription factor 3 (ATF3), a novel osteogenic transcription factor, in vascular smooth muscle cells. Both microRNA (miRNA) and mRNA microarrays were performed with rat vascular smooth muscle cells, and reciprocally regulated pairs of miRNA and mRNA were selected after bioinformatics analysis. Inorganic phosphate significantly reduced the expression of in A10 cells. The transcript level was also reduced in vitamin D-administered mouse aortas. reduced calcium deposition, whereas increased it. The Atf3 mRNA level was upregulated in a cellular vascular calcification model, and reduced the mRNA and protein levels. Transfection with could recover the -induced reduction of calcium deposition. Our results suggest that reduction of may contribute to the development of vascular calcification by de-repression of ATF3.