Association of the Inactive Circulating Matrix Gla Protein with Vitamin K Intake, Calcification, Mortality, and Cardiovascular Disease: A Review (Roumeliotis S et al.)

The authors of a narrative review published recently in the International Journal of Molecular Sciences, after having completed a thorough Medline database search, selected all trials that studied possible association of MGP forms and polymorphisms with vascular calcification, adverse events, and vitamin K supplementation. Matrix Gla Protein (MGP) is a vitamin K-dependent protein that is the first one to be recognized as an inhibitor of vascular calcification (VC) both in vitro and in vivo. This small protein is not only considered the most powerful natural inhibitor of calcification in the human body, but it can also reverse this dangerous process. High vitamin K2 intake can reverse both the inactivation of MGP and the acceleration of VC.

To become biologically active, MGP has to undergo γ-carboxylation of the Gla residues, followed by phosphorylation of the serine residues. Carboxylation and phosphorylation of MGP depend on vitamin K as their substrate. Only after carboxylation, MGP undergoes a biochemical change in its structure, crucial for its binding to bone morphogenetic protein-2 (BMP-2) and calcium crystals. Low levels of vitamin K2 (especially menaquinone-7, MK-7) result in various inactive forms of MGP, according to its state of carboxylation and/or phosphorylation: the uncarboxylated MGP (ucMGP), carboxylated but not phosphorylated MGP (dpcMGP), phosphorylated but uncarboxylated (pucMGP), and the fully inactive uncarboxylated, dephosphorylated MGP (dpucMGP), where the active form is both phosphorylated and carboxylated.

“The conclusion arrived at by the authors of this review article after analyzing a vast amount of studies, namely that supplementation of vitamin K2 (especially MK-7) seems to upregulate MGP activation and decrease the circulating inactive forms of MGP, continues to advocate the previous findings in this domain,” says Dr. Katarzyna Maresz, president of the International Science and Health Foundation. “It sends out a strong message to both healthy populations and patients that carry a heavy CV burden, that vitamin K2 intake might be very advantageous and effectively protect against future CV events,” she emphasizes.

References:

Roumeliotis S, Dounousi E, Eleftheriadis T, Liakopoulos V (2019) Association of the Inactive Circulating Matrix Gla Protein with Vitamin K Intake, Calcification, Mortality, and Cardiovascular Disease: A Review, International Journal of Molecular Sciences 20(3): 628, doi:10.3390/ijms20030628

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