Implication of a novel vitamin K dependent protein, GRP/Ucma in the pathophysiological conditions associated with vascular and soft tissue calcification, osteoarthritis, inflammation, and carcinoma

Bordoloi, Jijnasa; Dihingia, Anjum; Kalita, Jatin; Manna, Prasenjit

doi:10.1016/j.ijbiomac.2018.02.150

Cited by 16 publications

(17 citation statements)

References 99 publications

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“…Several studies have also implicated GRP in vascular and soft tissue calcification, osteoarthritis, inflammation and carcinoma (37). Similar to MGP, GRP inhibits phosphate-induced VSMC calcification via SMAD-dependent BMP signaling (38).…”

Section: Gla Proteinsmentioning

confidence: 99%

Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet

Bäck

Arányi

Cancela

et al. 2019

Front. Cardiovasc. Med.

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The physicochemical deposition of calcium-phosphate in the arterial wall is prevented by calcification inhibitors. Studies in cohorts of patients with rare genetic diseases have shed light on the consequences of loss-of-function mutations for different calcification inhibitors, and genetic targeting of these pathways in mice have generated a clearer picture on the mechanisms involved. For example, generalized arterial calcification of infancy (GACI) is caused by mutations in the enzyme ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (eNPP1), preventing the hydrolysis of ATP into pyrophosphate (PPi). The importance of PPi for inhibiting arterial calcification has been reinforced by the protective effects of PPi in various mouse models displaying ectopic calcifications. Besides PPi, Matrix Gla Protein (MGP) has been shown to be another potent calcification inhibitor as Keutel patients carrying a mutation in the encoding gene or Mgp-deficient mice develop spontaneous calcification of the arterial media. Whereas PPi and MGP represent locally produced calcification inhibitors, also systemic factors contribute to protection against arterial calcification. One such example is Fetuin-A, which is mainly produced in the liver and which forms calciprotein particles (CPPs), inhibiting growth of calcium-phosphate crystals in the blood and thereby preventing their soft tissue deposition. Other calcification inhibitors with potential importance for arterial calcification include osteoprotegerin, osteopontin, and klotho. The aim of the present review is to outline the latest insights into how different calcification inhibitors prevent arterial calcification both under physiological conditions and in the case of disturbed calcium-phosphate balance, and to provide a consensus statement on their potential therapeutic role for arterial calcification.

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Section: Gla Proteinsmentioning

confidence: 99%

Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet

Bäck

Arányi

Cancela

et al. 2019

Front. Cardiovasc. Med.

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“…VC has long been considered a passive and clinically irrelevant process resulting in the accumulation of mineral deposits in existent atherosclerotic intima plaques and/or the medial vessel wall [68,69]. However, increasing insights into the pathogenesis of VC have demonstrated that this specific type of ectopic mineralization is in fact an actively controlled multifactorial process and a major cause of cardiovascular disease worldwide [70].…”

Section: Acquired (Vascular) Calcification Disorders and Vitamin Kmentioning

confidence: 99%

“…Molecular alterations observed in VC pathogenesis include: I) Differentiation of VSMCs to an osteoblast-like phenotype; II) release of calcifying matrix vesicles rich in calcium and phosphate, but poor in mineralization inhibitors, like MGP; III) increased expression of osteochondrogenic markers, like BMP-2, Osterix (Osx), and RUNX2; and IV) decreased expression of calcification regulators, such as fetuin-A and ANKH (see above, PXE) and V), increased ER stress, and apoptosis [69,70,71].…”

Section: Acquired (Vascular) Calcification Disorders and Vitamin Kmentioning

confidence: 99%

“…In the last decade, a novel VKDP which may play an important role in VC has been discovered, namely Gla-rich protein (GRP), which has the highest density of Gla-residues of all known VKDPs, resulting in a high affinity for calcium [68]. Bordoloi et al [70] comprehensively reviewed the role of GRP in a variety of pathophysiological conditions, like ectopic mineralization, osteoarthritis, and breast carcinoma. In summary, increased uncarboxylated GRP (ucGRP) expression has been found at sites of osteogenic deposits, like in calcified aortic valves or PXE skin lesions, while carboxylated GRP (cGRP) was shown to inhibit VC to the same extent as cMGP [68,82].…”

Section: Acquired (Vascular) Calcification Disorders and Vitamin Kmentioning

confidence: 99%

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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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“…A recent review highlights the involvement of another vitamin Kedependent protein, Gla-rich protein or unique cartilage matrixeassociated protein, in regulating soft tissue and vascular calcification. 8 We are still left with several unanswered questions as practicing clinicians. Should all proximal violaceous painful nodular lesions be biopsied?…”

mentioning

confidence: 99%

Calciphylaxis in Patients With Preserved Renal Function: Worrisome Wounds

Albright

2018

Mayo Clinic Proceedings

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Implication of a novel vitamin K dependent protein, GRP/Ucma in the pathophysiological conditions associated with vascular and soft tissue calcification, osteoarthritis, inflammation, and carcinoma

Cited by 16 publications

References 99 publications

Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet

Endogenous Calcification Inhibitors in the Prevention of Vascular Calcification: A Consensus Statement From the COST Action EuroSoftCalcNet

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

Calciphylaxis in Patients With Preserved Renal Function: Worrisome Wounds

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