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The Inhibitory Roles of Vitamin K in Progression of Vascular Calcification

Department of Vascular Medicine and Vascular Science Center for Translational Research, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka 545-85858, Japan
Author to whom correspondence should be addressed.
Nutrients 2020, 12(2), 583;
Received: 26 December 2019 / Revised: 17 February 2020 / Accepted: 20 February 2020 / Published: 23 February 2020
(This article belongs to the Special Issue Vitamin K Intake and Human Health)
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. View Full-Text
Keywords: atherosclerosis; matrix Gla protein; oncostatin M; vascular calcification atherosclerosis; matrix Gla protein; oncostatin M; vascular calcification
MDPI and ACS Style

Shioi, A.; Morioka, T.; Shoji, T.; Emoto, M. The Inhibitory Roles of Vitamin K in Progression of Vascular Calcification. Nutrients 2020, 12, 583.

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