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Extrahepatic Vitamin K-Dependent Gla-Proteins-Potential Cardiometabolic Biomarkers
Bistra Galunska1, Yoto Yotov2,3, Miglena Nikolova1
1Department of Biochemistry Molecular Medicine and Nutrigenomics, Medical University of Varna, 9000 Varna, Bulgaria.
Abstract:
One mechanism to regulate pathological vascular calcification (VC) is its active inhibition. Loss or inactivation of endogenic inhibitors is a major inductor of VC. Such inhibitors are proteins rich in gamma-glutamyl residues (Gla-proteins), whose function strongly depends on vitamin K. The current narrative review is focused on discussing the role of extrahepatic vitamin K-dependent Gla-proteins (osteocalcin, OC; matrix Gla-protein, MGP; Gla-rich protein, GRP) in cardio-vascular pathology. Gla-proteins possess several functionally active forms whose role in the pathogenesis of VC is still unclear. It is assumed that low circulating non-phosphorylated MGP is an indicator of active calcification and could be a novel biomarker of prevalent VC. High circulating completely inactive MGP is proposed as a novel risk factor for cardio-vascular events, disease progression, mortality, and vitamin K deficiency. The ratio between uncarboxylated (ucOC) and carboxylated (cOC) OC is considered as an indicator of vitamin K status indirectly reflecting arterial calcium. Despite the evidence that OC is an important energy metabolic regulator, its role on global cardio-vascular risk remains unclear. GRP acts as a molecular mediator between inflammation and calcification and may emerge as a novel biomarker playing a key role in these processes. Gla-proteins benefit clinical practice as inhibitors of VC, modifiable by dietary factors.
Insights
Vitamin K-dependent Gla-proteins inhibit vascular calcification. Inactive forms of matrix Gla-protein (MGP) and osteocalcin (OC) indicate calcification and cardiovascular risk.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Nutritional Science
Background:
- Pathological vascular calcification (VC) is regulated by active inhibition.
- Loss or inactivation of endogenous inhibitors, particularly vitamin K-dependent Gla-proteins, induces VC.
- Extrahepatic vitamin K-dependent Gla-proteins (osteocalcin (OC), matrix Gla-protein (MGP), Gla-rich protein (GRP)) are crucial in cardiovascular pathology.
Purpose of the Study:
- To review the role of extrahepatic vitamin K-dependent Gla-proteins in cardiovascular pathology.
- To discuss the significance of different Gla-protein forms in VC pathogenesis.
- To explore potential novel biomarkers for VC and cardiovascular events.
Main Methods:
- Narrative review of existing literature.
- Analysis of the functional roles of OC, MGP, and GRP in VC.
- Evaluation of circulating Gla-protein forms as indicators of VC and cardiovascular risk.
Main Results:
- Low non-phosphorylated MGP may indicate active calcification and serve as a VC biomarker.
- High inactive MGP is linked to cardiovascular events, disease progression, mortality, and vitamin K deficiency.
- The ucOC/cOC ratio reflects vitamin K status and arterial calcification; OC's role in global cardiovascular risk is unclear.
- GRP mediates inflammation and calcification, potentially emerging as a key biomarker.
Conclusions:
- Vitamin K-dependent Gla-proteins are vital inhibitors of VC.
- Specific circulating forms of MGP, OC, and GRP show promise as biomarkers for VC and cardiovascular risk.
- Dietary factors modifying Gla-proteins offer potential clinical benefits for managing VC.
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