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Figure 1. The vessel wall is organized into 3 layers. The intimal layer is made up of one layer of endothelial cells and the internal elastic lamina. The medial layer of a healthy vessel consists of contractile vascular smooth muscle cells (VSMCs), the extracellular matrix (ECM), and elastic fibers. The adventitia is the outer layer of connective tissue. Vascular calcification can occur at the intimal and medial layers with different risk factors and outcomes. Intimal calcification is commonly associated with atherosclerosis and is characterized by formation of a plaque with a fibrous cap and accumulation of lipids and inflammatory cells. Medial calcification often results in arteriosclerosis and vascular stiffening. VSMCs are the main mediators of medial calcification and can undergo phenotypic differentiation into a more synthetic, osteoblast-like phenotype, characterized by extracellular matrix (ECM) remodeling and extracellular vesicle (EV) secretion. (Created with BioRender.com)