Vitamin K‑dependent proteins involved in bone and cardiovascular health (Review)

Abstract

In postmenopausal women and elderly men, bone density decreases with age and vascular calcification is aggravated. This condition is closely associated with vitamin K2 deficiency. A total of 17 different vitamin K-dependent proteins have been identified to date. Vitamin K-dependent proteins are located within the bone, heart and blood vessels. For instance, carboxylated osteocalcin is beneficial for bone and aids the deposition of calcium into the bone matrix. Carboxylated matrix Gla protein effectively protects blood vessels and may prevent calcification within the vascular wall. Furthermore, carboxylated Gla-rich protein has been reported to act as an inhibitor in the calcification of the cardiovascular system, while growth arrest-specific protein-6 protects endothelial cells and vascular smooth muscle cells, resists apoptosis and inhibits the calcification of blood vessels by inhibiting the apoptosis of vascular smooth muscle cells. In addition, periostin may promote the differentiation, aggregation, adhesion and proliferation of osteoblasts. Periostin also occurs in the heart and may be associated with the reconstruction of heart function. These vitamin K-dependent proteins may exert their functions following γ-carboxylation with vitamin K, and different vitamin K-dependent proteins may exhibit synergistic effects or antagonistic effects on each other. In the cardiovascular system with vitamin K antagonist supplement or vitamin K deficiency, calcification occurs in the endothelium of blood vessels and vascular smooth muscle cells are transformed into osteoblast-like cells, a phenomenon that resembles bone growth. Both the bone and cardiovascular system are closely associated during embryonic development. Thus, the present study hypothesized that embryonic developmental position and tissue calcification may have a certain association for the bone and the cardiovascular system. This review describes and briefly discusses several important vitamin K-dependent proteins that serve an important role in bone and the cardiovascular system. The results of the review suggest that the vascular calcification and osteogenic differentiation of vascular smooth muscle cells may be associated with the location of the bone and cardiovascular system during embryonic development.

Engineering Lactococcus lactis for Increased Vitamin K2 Production

“…This enzyme carboxylates glutamine residues on certain proteins into γ-carboxyglutamic acid (Gla) residues. Gla-proteins have increased affinity for calcium and are involved in protein-protein interactions (through Ca 2+ ), cell membrane interactions and processes that promote correct deposition of calcium in bone and prevents deposition in soft tissues like arteries, cartilage, and heart valves (Wen et al, 2018).…”

The Role of Vitamin D in Modulating Mesenchymal Stem Cells and Endothelial Progenitor Cells for Vascular Calcification

“…Under vitamin K sufficient status, phosphorylated MGP also avoided osteoblastic changes of VSMCs [69]. Mature MGP formed mineralized complex with fetuin-A, calcium, and phosphorus ion to lessen the mineral composition within vessels ( Figure 1) [70]. In CKD patients, the secondary CPP was associated with insufficient MGP [71].…”

Vitamin K and Bone Health: A Review on the Effects of Vitamin K Deficiency and Supplementation and the Effect of Non-Vitamin K Antagonist Oral Anticoagulants on Different Bone Parameters

“…With the exception of MK-4, all MK subtypes are synthesized by bacteria present in the human gut (mainly bacteroides in the large intestine, which mostly produce MK 10-13) [4] or bacteria present in some foods including animal liver and fermented foods (mainly cheese in Western countries, and natto, a soybean-based food in Japan). Natto is especially rich in MK-7, which has the highest bioactivity and half-life compared to PK and MK-4 [5,6]. Long-chain MK produced by enteric flora have low bioactivity.…”