Vascular calcification is a frequent complication of atherosclerosis, diabetes, and chronic kidney disease. In the latter group of patients, calcification is commonly seen in tunica media where smooth muscle cells (SMC) undergo osteoblastic transformation. Risk factors such as elevated phosphorus levels and vitamin D3 analogs have been identified. Inlight of earlier observations by our group and others, we sought to inhibit SMC calcification via induction of ferritin. Human aortic SMC were cultured using β-glycerophosphate with activated vitamin D3, or inorganic phosphate with calcium, and induction of alkaline phosphatase and osteocalcin as well as accumulation of calcium were used to monitor osteoblastic transformation. Additionally, to examine the role of vitamin D3 analogs, plasma samples from patients on hemodialysis who hadreceived calcitriol or paricalcitol were tested for their tendency to induce calcification of SMC. Addition of exogenous ferritin mitigates the transformation of SMC into osteoblast-like cells. Importantly, pharmacologic induction of heavy chain ferritin by 3H-1,2-Dithiole-3-thione was able to inhibit the SMC transition into osteoblast-like cells and calcification of extracellular matrix. Plasma samples collected from patients after administration of activated vitamin D3 caused significantly increased alkaline phosphatase activity in SMC compared to samples drawn prior to activated vitamin D3 and here, again induction of ferritin diminished the osteoblastic transformation. Our data suggests that pharmacologic induction of ferritin prevents osteoblastic transformation of SMC. Hence, utilization of such agents thatwill cause enhanced ferritin synthesis may have important clinical application in prevention of vascular calcification
