Serum total matrix Gla protein: Reference interval in healthy adults and variations in patients with vascular and osteoarticular diseases

Silaghi, Cristina Alina; Fodor, Daniela; Gheorghe, Simona; Crăciun, Alexandra

doi:10.1016/j.cca.2018.12.029

Cited by 11 publications

(10 citation statements)

References 23 publications

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Section: Acquired (Vascular) Calcification Disorders and Vitamin Kmentioning

confidence: 92%

“…A recently published study by Silaghi et al [78] further established the role of increased MGP expression in VC pathophysiology by demonstrating significantly higher serum total MGP concentrations in patients with vascular diseases compared to healthy controls (106 vs. 51 µg/L, p < 0.001). This finding definitely warrants further research as the serum total MGP may thus serve as a biomarker that can reliably discriminate between healthy individuals and VC-affected patients, independent of associated traditional cardiovascular risk factors, such as smoking [78]. Additionally, the novel T50-test, which determines the transformation time point, T50, from amorphous to crystalline calciprotein particles (transporting calcium, phosphate and calcification-inhibiting proteins in serum) in artificially supersaturated serum, has proven to be closely associated with aortic stiffening and cardiovascular mortality and may thus potentially be used in the future to guide clinical decision making and therapeutic strategies in patients with a high systemic calcification propensity [79].…”

Section: Acquired (Vascular) Calcification Disorders and Vitamin Kmentioning

confidence: 92%

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The Role of Vitamin K and Its Related Compounds in Mendelian and Acquired Ectopic Mineralization Disorders

Nollet

Gils

Verschuere

et al. 2019

IJMS

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Ectopic mineralization disorders comprise a broad spectrum of inherited or acquired diseases characterized by aberrant deposition of calcium crystals in multiple organs, such as the skin, eyes, kidneys, and blood vessels. Although the precise mechanisms leading to ectopic calcification are still incompletely known to date, various molecular targets leading to a disturbed balance between pro- and anti-mineralizing pathways have been identified in recent years. Vitamin K and its related compounds, mainly those post-translationally activated by vitamin K-dependent carboxylation, may play an important role in the pathogenesis of ectopic mineralization as has been demonstrated in studies on rare Mendelian diseases, but also on highly prevalent disorders, like vascular calcification. This narrative review compiles and summarizes the current knowledge regarding the role of vitamin K, its metabolism, and associated compounds in the pathophysiology of both monogenic ectopic mineralization disorders, like pseudoxanthoma elasticum or Keutel syndrome, as well as acquired multifactorial diseases, like chronic kidney disease. Clinical and molecular aspects of the various disorders are discussed according to the state-of-the-art, followed by a comprehensive literature review regarding the role of vitamin K in molecular pathophysiology and as a therapeutic target in both human and animal models of ectopic mineralization disorders.

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Section: Acquired (Vascular) Calcification Disorders and Vitamin Kmentioning

confidence: 92%

Section: Acquired (Vascular) Calcification Disorders and Vitamin Kmentioning

confidence: 92%

The Role of Vitamin K and Its Related Compounds in Mendelian and Acquired Ectopic Mineralization Disorders

Nollet

Gils

Verschuere

et al. 2019

IJMS

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“…It is not clear if serum MGP levels, mainly attributed to the inactive dp-ucMGP, are influenced directly by kidney disfunction or more so by vitamin K insufficiency. The cross-sectional and cohort studies only assessed dp-ucMGP levels in CKD, but not serum levels of total MGP [94]. The increase in dp-ucMGP levels might only be a shift in the ratio of active versus inactive forms of MGP, with total MGP levels remaining unchanged.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, dephospho-uncarboxylated MGP (dp-ucMGP), the inactive conformation, was associated with increased VC in patients with ESRD [12]. There are also available assays that cannot discriminate between different conformations of MGP, designated as total MGP (t-MGP); however, these assays have not yet been studied in CKD [94].…”

Section: Functional and Molecular Backgroundmentioning

confidence: 99%

Vitamin K Dependent Proteins in Kidney Disease

Silaghi

Ilyés

Filip

et al. 2019

IJMS

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Patients with chronic kidney disease (CKD) have an increased risk of developing vascular calcifications, as well as bone dynamics impairment, leading to a poor quality of life and increased mortality. Certain vitamin K dependent proteins (VKDPs) act mainly as calcification inhibitors, but their involvement in the onset and progression of CKD are not completely elucidated. This review is an update of the current state of knowledge about the relationship between CKD and four extrahepatic VKDPs: matrix Gla protein, osteocalcin, growth-arrest specific protein 6 and Gla-rich protein. Based on published literature in the last ten years, the purpose of this review is to address fundamental aspects about the link between CKD and circulating VKDPs levels as well as to raise new topics about how the interplay between molecular weight and charge could influence the modifications of circulating VKDPs at the glomerular level, or whether distinct renal etiologies have effect on VKDPs. This review is the output of a systematic literature search and may open future research avenues in this niche domain.

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“…Apart from the specific determination of undercarboxylated MGP, also total MGP has been found to be positively associated with the presence of vascular disease (mainly coronary artery disease or hypertension) [107]. Whether this just reflects a high total ucMGP or a defense attempt [108] requires additional research.…”

Section: Matrix Gla Protein and Vitamin K Statusmentioning

confidence: 99%

Modifying Phosphate Toxicity in Chronic Kidney Disease

Vervloet

2019

Toxins

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Phosphate toxicity is a well-established phenomenon, especially in chronic kidney disease (CKD), where hyperphosphatemia is a frequent occurrence when CKD is advanced. Many therapeutic efforts are targeted at phosphate, and comprise dietary intervention, modifying dialysis schemes, treating uncontrolled hyperparathyroidism and importantly, phosphate binder therapy. Despite all these interventions, hyperphosphatemia persists in many, and its pathological influence is ongoing. In nephrological care, a somewhat neglected aspect of treatment—when attempts fail to lower exposure to a toxin like phosphate—is to explore the possibility of “anti-dotes”. Indeed, quite a long list of factors modify, or are mediators of phosphate toxicity. Addressing these, especially when phosphate itself cannot be sufficiently controlled, may provide additional protection. In this narrative overview, several factors are discussed that may qualify as either such a modifier or mediator, that can be influenced by other means than simply lowering phosphate exposure. A wider scope when targeting phosphate-induced comorbidity in CKD, in particular cardiovascular disease, may alleviate the burden of disease that is the consequence of this potentially toxic mineral in CKD.

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Serum total matrix Gla protein: Reference interval in healthy adults and variations in patients with vascular and osteoarticular diseases

Cited by 11 publications

References 23 publications

The Role of Vitamin K and Its Related Compounds in Mendelian and Acquired Ectopic Mineralization Disorders

The Role of Vitamin K and Its Related Compounds in Mendelian and Acquired Ectopic Mineralization Disorders

Vitamin K Dependent Proteins in Kidney Disease

Modifying Phosphate Toxicity in Chronic Kidney Disease

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