The Inhibitory Roles of Vitamin K in Progression of Vascular Calcification

• Published in: Nutrients Vol. 12; no. 2; p. 583
• Main Authors: Shioi, Atsushi, Morioka, Tomoaki, Shoji, Tetsuo, Emoto, Masanori
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.02.2020; MDPI
• Subjects: Animals; Anticoagulants; Apoptosis; Arteriosclerosis; Atherosclerosis; Biomarkers; Biomarkers - blood; Biomedical materials; Calcification; Calcification (ectopic); Carboxylation; Cardiovascular diseases; Cardiovascular Diseases - blood; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - mortality; Cardiovascular Diseases - pathology; Cartilage; Cell differentiation; Clinical trials; Cytokines; Diabetes; Disease Progression; Humans; IL-1β; In vivo methods and tests; Inflammation; Inflammation - blood; Inflammation - drug therapy; Inflammation - pathology; Interleukin 6; Kinases; Ligands; Macrophages; matrix gla protein; Mineralization; Mortality; Muscles; NF-κB protein; Oncostatin M; Osteoblastogenesis; Osteoblasts; Oxidative stress; Phylloquinone; Plasma; Proteins; Review; Signal transduction; Smooth muscle; Soft tissues; Stem cells; Tumor necrosis factor-TNF; Tumor necrosis factor-α; vascular calcification; Vascular Calcification - blood; Vascular Calcification - drug therapy; Vitamin deficiency; Vitamin K; Vitamin K - therapeutic use; Warfarin; atherosclerosis; matrix Gla protein; oncostatin M; vascular calcification
• ISSN: 2072-6643; 2072-6643
• 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.