Fig. 1.

Role of vascular smooth muscle cells in vascular calcification. Following exposure to pro-calcific factors, most importantly hyperphosphatemia, vascular smooth muscle cells (VSMCs) are able to transdifferentiate into an osteo-/chondrogenic phenotype. This process is characterized and, at least partly, mediated by expression of osteogenic transcription factors such as CBFA1, MSX2, SOX9, and osterix. The osteo-/chondroblast-like cells actively promote calcification by reduced availability of calcification inhibitors, apoptosis, and apoptotic body release as well as release of calcifying extracellular vesicles, remodeling of the extracellular matrix and elastin degradation, and a pro-inflammatory state with release of pro-inflammatory cytokines and oxidative stress. These create a pro-calcifying environment, which allows for active mineralization of the vasculature