The type of vascular calcification associated with diabetes and ESRD is histologically distinct from that found in atherosclerotic plaques. In patients with CKD or diabetes calcium deposits are concentric and uniformly distributed within the medial layer of the vessel wall. The deposition of calcium does not require the presence of atherosclerotic lesions and occurs in the absence of intimal hyperplasia. Infiltration of the adventia by T cells and activated macrophages leads to expression of bone morphogenetic protein 2 (BMP-2) and osteopontin (OPN) by pericytic myofibroblasts. In diabetics, BMP-2 expression is enhanced by the simultaneous upregulation of two BMP-2 associated transcription factors Msx1 and Msx2 3. The resulting transcription of BMP-2 genes leads to mineralization of non-endochondrial matrix. The expression of OPN is a consistent feature of medial calcification 4. Osteopontin or "bone bridge" is a highly phosphorylated glycoprotein that binds calcium and integrin receptors. The expression of osteopontin can be stimulated by vitamin D and increased circulating levels of phosphate.