Involvement of Vitamin K

Vascular calcification results from an imbalance of promoters and inhibitors of mineralization in the vascular wall, culminating in the creation of an organized extracellular matrix deposition. It is characterized by the accumulation of calcium phosphate complex and crystallization of hydroxyapatite in the tunica media, leading to vessel stiffening. The underlying initiators of dysregulated calcification maintenance are diverse. These range from the expression of bone-associated proteins, to the osteogenic transdifferentiation of smooth muscle cells to osteoblast-like cells, to the release of fragmented apoptotic bodies and mineralization competent extracellular vesicles by smooth muscle cells, which act as a nucleation site for the deposition of hydroxyapatite crystals. The process involves a complex interplay between vitamin K-dependent calcification-inhibitory proteins, such as matrix γ-carboxyglutamate acid (Gla) protein, Gla-rich protein and growth arrest-specific gene 6 protein, and stimulatory mediators, such as osteocalcin. Vitamin K plays an important role as a cofactor for posttranslational γ-carboxylation of matrix Gla proteins in converting to a biologically active conformation. Drugs that inhibit vitamin K, such as warfarin, impair γ-carboxylation of Gla proteins, resulting in the accumulation of uncarboxylated proteins lacking calcification-inhibitory capacity. This article overviews the involvement of systemically and locally expressed vitamin K-dependent proteins in vascular calcification and their potential as biomarkers of calcification