1. Volume 83, Issue 5, Pages 782-784 (May 2013)
Vitamin K: key vitamin in controlling vascular calcification in chronic kidney disease 
Leon J. Schurgers 
Kidney International 
Volume 83, Issue 5, Pages (May 2013)
DOI: /ki
Copyright © 2013 International Society of Nephrology Terms and Conditions

2. Figure 1
Vascular smooth muscle cells (VSMCs) synthesize matrix Gla protein (MGP), and in the presence of sufficient vitamin K, MGP is produced in its carboxylated form and is thereby able to prevent mineralization. Contractile VSMCs have a fully functional machinery to synthesize carboxylated MGP (cMGP), thereby keeping them—and the extracellular matrix (ECM)—free of calcification stress. In chronic kidney disease (CKD), the uremic environment (high calcium, high phosphate, oxidative stress) causes VSMCs to differentiate from contractile to synthetic/proliferative VSMCs, enabling them to cope with the uremic environment. In the presence of vitamin K, cMGP inhibits BMP2-driven VSMC transdifferentiation toward an osteochondrogenic phenotype. Moreover, cMGP loaded in matrix vesicles controls and inhibits extracellular matrix calcification. In the case of vitamin K deficiency, MGP is not carboxylated, resulting in undercarboxylated MGP (ucMGP). The high phosphate and uremic environment are not counterbalanced by MGP, and VSMCs become osteochondrogenic. Osteochondrogenic VSMCs in turn produce less MGP and start synthesizing bone-associated proteins, such as alkaline phosphatase. Moreover, they are susceptible to apoptosis, and secrete more matrix vesicles and apoptotic bodies, resulting in extracellular mineralization, which further accelerates apoptosis of VSMCs.
Kidney International  , DOI: ( /ki )
Copyright © 2013 International Society of Nephrology Terms and Conditions