The Inhibitory Roles of Vitamin K in Progression of Vascular Calcification

Nutrients. 2020 Feb 23;12(2):583. doi: 10.3390/nu12020583.


Vitamin K is a fat-soluble vitamin that is indispensable for the activation of vitamin K-dependent proteins (VKDPs) and may be implicated in cardiovascular disease (CVD). Vascular calcification is intimately associated with CV events and mortality and is a chronic inflammatory process in which activated macrophages promote osteoblastic differentiation of vascular smooth muscle cells (VSMCs) through the production of proinflammatory cytokines such as IL-1β, IL-6, TNF-α, and oncostatin M (OSM) in both intimal and medial layers of arterial walls. This process may be mainly mediated through NF-κB signaling pathway. Vitamin K has been demonstrated to exert anti-inflammatory effects through antagonizing NF-κB signaling in both in vitro and in vivo studies, suggesting that vitamin K may prevent vascular calcification via anti-inflammatory mechanisms. Matrix Gla protein (MGP) is a major inhibitor of soft tissue calcification and contributes to preventing both intimal and medial vascular calcification. Vitamin K may also inhibit progression of vascular calcification by enhancing the activity of MGP through facilitating its γ-carboxylation. In support of this hypothesis, the procalcific effects of warfarin, an antagonist of vitamin K, on arterial calcification have been demonstrated in several clinical studies. Among the inactive MGP forms, dephospho-uncarboxylated MGP (dp-ucMGP) may be regarded as the most useful biomarker of not only vitamin K deficiency, but also vascular calcification and CVD. There have been several studies showing the association of circulating levels of dp-ucMGP with vitamin K intake, vascular calcification, mortality, and CVD. However, additional larger prospective studies including randomized controlled trials are necessary to confirm the beneficial effects of vitamin K supplementation on CV health.

Keywords: atherosclerosis; matrix Gla protein; oncostatin M; vascular calcification.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / pathology
  • Disease Progression*
  • Humans
  • Inflammation / blood
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Vascular Calcification / blood
  • Vascular Calcification / drug therapy*
  • Vitamin K / therapeutic use*


  • Biomarkers
  • Vitamin K