The Inhibitory Roles of Vitamin K in Progression of Vascular Calcification.

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Shioi A, Morioka T, Shoji T, Emoto M

The Inhibitory Roles of Vitamin K in Progression of Vascular Calcification.

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

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32102248 [ View in PubMed
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Abstract

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-1beta, IL-6, TNF-alpha, and oncostatin M (OSM) in both intimal and medial layers of arterial walls. This process may be mainly mediated through NF-kappaB signaling pathway. Vitamin K has been demonstrated to exert anti-inflammatory effects through antagonizing NF-kappaB 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 gamma-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.

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