期刊
NUTRIENTS
卷 12, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/nu12020583
关键词
atherosclerosis; matrix Gla protein; oncostatin M; vascular calcification
资金
- Japan Society for the promotion of Science [17K09731]
- Grants-in-Aid for Scientific Research [17K09731] Funding Source: KAKEN
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-1 beta, 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-kappa B signaling pathway. Vitamin K has been demonstrated to exert anti-inflammatory effects through antagonizing NF-kappa B 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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