Circulating Dephospho-Uncarboxylated Matrix Gla-Protein Is Associated With Kidney Dysfunction and Arterial Stiffness

Puzantian, Houry; Akers, Scott; Oldland, Garrett; Javaid, Khuzaima; Miller, Rachana; Ge, Yueya; Ansari, Bilal; Lee, Jonathan J.; Suri, Arpita; Hasmath, Zeba; Townsend, Raymond R.; Chirinos, Julio A.

doi:10.1093/ajh/hpy079

Cited by 59 publications

(59 citation statements)

References 22 publications

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“…There is some data showing that dp-ucMGP is associated with several micro and macrovascular complications of diabetes, including diabetic nephropathy, retinopathy, vascular stiffness and vascular calcification [39][40][41]. Although dp-ucMGP has been repeatedly associated with vascular calcification and cardiovascular disease, dp-ucMGP is not associated in our study with coronary arterial disease (S1 Table) [39,41].…”

Section: Discussioncontrasting

confidence: 50%

Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes

et al. 2020

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Aims/Hypothesis Diabetic peripheral neuropathy is a frequent and severe complication of diabetes. As Matrixgla-protein (MGP) is expressed in several components of the nervous system and is involved in some neurological disease, MGP could play a role in peripheral nervous system homeostasis. The aim of this study was to evaluate factors associated with sensitive diabetic neuropathy in Type 2 Diabetes, and, in particular, dephospho-uncarboxylated MGP (dp-ucMGP), the inactive form of MGP. Methods 198 patients with Type 2 Diabetes were included. Presence of sensitive diabetic neuropathy was defined by a neuropathy disability score (NDS) �6. Plasma levels of dp-ucMGP were measured by ELISA.

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Section: Discussioncontrasting

confidence: 50%

Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes

et al. 2020

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“…Results of a cohort study showed that kidney transplant recipients at the highest quartile of dp-ucMGP had a higher risk of developing transplant failure and mortality risk (13). Recently, Puzantian et al significantly reported that dp-ucMGP level was progressively increased in CKD patients with decreasing renal function (35). However, according to our results, the association of serum dp-ucMGP with kidney function was not statistically significant.…”

Section: Discussioncontrasting

confidence: 76%

“…It seems that micro-vascular dysregulation of kidney such as micro-albuminuria is inversely related to the circulating level of vitamin K and activated MGP levels (19). There is some evidence that serum level of dp-ucMGP is directly related to proteinuria and serum creatinine and inversely related to renal function (GFR, glomerular filtration rate) in patients with CKD (20)(21)(22)(23)(24)(25)(26).…”

Section: Article Typementioning

confidence: 99%

The association of serum dephosphorylated-uncarboxylated matrix gamma carboxyglutamate protein (dp-ucMGP) as a marker of vascular vitamin K status with allograft function in kidney transplant recipients

et al. 2019

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Implication for health policy/practice/research/medical education:In a study on 90 kidney transplant recipients in the post-transplant phase, we found, the mean serum level of dephosphorylateduncarboxylated matrix gamma carboxyglutamate protein (dp-ucMGP) was in normal range. However, a small percentage of participants had high serum dp-ucMGP (>12 µg/L). Serum dp-ucMGP did not have any statistical significant association with serum urea, creatinine and kidney function, since previous studies showed high serum level of dp-ucMGP may make kidney transplant recipients susceptible to the cardiovascular events and transplant rejection. Please cite this paper as: Ebrahimzadeh Attari V, Shahvegharasl Z, Fathalizadeh P, Pourasghary S, Mohajel Shoja M, Niknafs B, Ardalan M. The association of serum dephosphorylated-uncarboxylated matrix gamma carboxyglutamate protein (dp-ucMGP) as a marker of vascular vitamin K status with allograft function in kidney transplant recipients. J Nephropathol. 2020;9(3):e24.

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“…Since MGP is an active inhibitor of VC it could be a potential useful biomarker. Indeed, circulating plasma levels of dp-ucMGP correlate with amount of VC 22,23 and arterial stiffness 26 . In accordance, we report that patients with the highest dp-ucMGP levels had a higher CAC score and more extensive medial VC.…”

Section: High Calcification Score Media (Q2 + Q3)mentioning

confidence: 99%

Matrix Gla protein is an independent predictor of both intimal and medial vascular calcification in chronic kidney disease

Jaminon

Dai

Qureshi

et al. 2020

Sci Rep

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Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification (VC) and requires carboxylation by vitamin K to exert calcification inhibition. Chronic kidney disease (CKD) patients undergo early vascular aging often involving extensive VC. The present cross-sectional study investigated the association between circulating dp-ucMGP levels, MGP expression in vascular tissue and MGP polymorphisms. In 141 CKD stage 5 patients, CAC score was significantly increased in the highest tertile of dp-ucMGP (p = 0.002), and a high medial VC score was associated with elevated dp-ucMGP levels. MGP vascular expression was associated with increased circulating dp-ucMGP and CAC scores. MGP SNP analysis revealed that patients homozygous for the C allele of the rs1800801 variant had a higher CAC score (median 15 [range 0-1312]) compared to patients carrying a T allele (median 0 [range 0-966] AU). These results indicate that plasma levels of dp-ucMGP are an independent predictor of increased VC in CKD5 patients and correlate with both higher CAC scores and degree of medial calcification. Additionally, high vascular expression of MGP was associated with higher CAC scores and plasma dp-ucMGP levels. Taken together, our results support that MGP is involved in the pathogenesis of VC. Matrix Gla protein (MGP) is a vitamin K dependent protein (VKDP) that is involved in the inhibition of vascular calcification (VC). MGP is small secretary protein (14 kD) that is primarily secreted by vascular smooth muscle cells (VSMCs) in the arterial wall 1. MGP contains five Glu residues that require carboxylation to become activated and to fulfill its calcification inhibitory function. This carboxylation step cannot take place in the absence of vitamin K, which has an unequivocal role in driving this post-translational step 2,3. Vitamin K is a co-factor for the enzyme γ-glutamyl carboxylase that converts glutamic acid (Glu) into γ-carboxyglutamic acid (Gla) residues 2. This conversion is critical for the activation of MGP. Additionally, there are three serine residues that need phosphorylation 4,5. The exact role of phosphorylation of MGP is still not known, but it is believed to play an important role in the regulation of secretion of the protein 3. Upon activation, MGP binds calcium-salts with high affinity, thereby affecting the calcification processes. The importance of MGP in the inhibition of calcification is illustrated by studies of MGP knockout mice, who die within two months after birth due to severe arterial calcification and rupture of the aorta 1. Chronic kidney disease (CKD) patients have an extremely high risk for developing vascular disease 4. VC, manifested both as medial and intimal calcification with distinct pathologies, is a common risk factor in CKD 5. Additionally, vitamin K deficiency is frequently encountered in CKD, which is associated with increased plasma levels of dephosphorylated uncarboxylated MGP (dp-ucMGP) plasma levels 6,7. Furthermore, increased plasma dp-ucMGP

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Circulating Dephospho-Uncarboxylated Matrix Gla-Protein Is Associated With Kidney Dysfunction and Arterial Stiffness

Cited by 59 publications

References 22 publications

Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes

Inactive matrix gla protein plasma levels are associated with peripheral neuropathy in Type 2 diabetes

The association of serum dephosphorylated-uncarboxylated matrix gamma carboxyglutamate protein (dp-ucMGP) as a marker of vascular vitamin K status with allograft function in kidney transplant recipients

Matrix Gla protein is an independent predictor of both intimal and medial vascular calcification in chronic kidney disease

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