Vascular calcification

Vascular calcification is an active, cell-regulated process in which hydroxyapatite deposits within the arterial wall, not a passive precipitation as once assumed. Two mechanistically distinct forms exist: intimal calcification within atherosclerotic plaques, driven by inflammation, macrophage infiltration, and VSMC apoptosis; and medial calcification (Mönckeberg sclerosis), which forms in the tunica media independently of lipid accumulation and is linked to aging, diabetes, and chronic kidney disease. In both forms, VSMCs undergo osteogenic transdifferentiation, upregulating BMP-2, BMP-4, and Runx2 while losing contractile identity (Durham et al. 2018). Matrix Gla Protein (MGP), a vitamin K-dependent VSMC-secreted inhibitor, acts as an endogenous brake; γ-carboxylation is required for MGP to sequester calcium and BMPs, and insufficient vitamin K2 generates inactive dp-ucMGP — a plasma biomarker correlating with calcification burden and cardiovascular risk (Barrett et al. 2018). Medial calcification raises arterial stiffness, pulse-wave velocity, and left-ventricular afterload — an independent predictor of cardiovascular mortality in older adults, though interventional evidence remains limited.