Calcification mechanisms in native atherosclerotic arteries

Vascular Calcification, i.e., the ectopic accumulation of calcium phosphate salts in the vessel wall, is associated with atherosclerosis, aging, diabetes, and chronic kidney disease, which thusly contributes to increased cardiovascular morbidity and mortality. Previously considered to be a passive process, vascular calcification is now recognized as an active process similar to bone formation. However, the pathogenetic mechanisms involved in vascular calcification are particularly complex and remain inadequately understood, even though they impact significantly on patient prognosis as well as on the stenting placement and outcome of revascularization. Cellular, subcellular, genetic and molecular mechanisms have been proposed. Of particular importance is the role of the progenitor cells either resident in the vessel wall or circulating that are committed to an osteogenic program as well as transdifferentiation of vascular smooth-muscle cells. In addition, numerous evidences show that metastatic calcification is not as directly related to atherosclerosis as dystrophic is, indicating another mechanism of generation, involving additional metabolic pathways. A better understanding of the pathogenetic mechanisms corroborated with ultrastructural clues, as shown in the present review, will be essential for the development of new therapeutic strategies, in order to prevent and treat vascular calcification.