Figure 3. The vascular calcification-inflammation cycle. Calcium-phosphate (CaP) mineral is present in secondary calciprotein particles (CPP-II), in calcifying extracellular vesicles (cEVs) and in the extracellular matrix (ECM) of blood vessels. All these forms of CaP mineral are able to induce pro-inflammatory responses in immune and VSMs cells, and the osteogenic differentiation of VSMCs. In turn, macrophage pro-inflammatory responses contribute to increased vascular calcification through the release of cEVs and inducing osteogenic differentiation of VSMCs, while osteogenic VSMCs drive ECM calcification through the release of cEVs and increase in macrophage pro-inflammatory responses, in a vicious cycle.