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

Armand M. G. Jaminon; Lu Dai; Abdul Rashid Qureshi; Pieter Evenepoel; Jonaz Ripsweden; Magnus Soderberg; Anna Witasp; Hannes Olauson; Leon J. Schurgers; Peter Stenvinkel

doi:10.1038/s41598-020-63013-8

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

Armand M. G. Jaminon, Lu Dai, Abdul Rashid Qureshi, Pieter Evenepoel, Jonaz Ripsweden, Magnus Soderberg, Anna Witasp, Hannes Olauson, Leon J. Schurgers, Peter Stenvinkel^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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.

Original language	English
Article number	6586
Number of pages	9
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-63013-8
Publication status	Published - 20 Apr 2020

Keywords

STAGE RENAL-DISEASE
CORONARY-ARTERY CALCIFICATION
CARDIOVASCULAR EVENTS
RISK
SUPPLEMENTATION
OSTEOCALCIN
EXPRESSION
MARKER

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@article{76acec4f654f42b3b63267e0701dfb88,

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

abstract = "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.",

keywords = "STAGE RENAL-DISEASE, CORONARY-ARTERY CALCIFICATION, CARDIOVASCULAR EVENTS, RISK, SUPPLEMENTATION, OSTEOCALCIN, EXPRESSION, MARKER",

author = "Jaminon, {Armand M. G.} and Lu Dai and Qureshi, {Abdul Rashid} and Pieter Evenepoel and Jonaz Ripsweden and Magnus Soderberg and Anna Witasp and Hannes Olauson and Schurgers, {Leon J.} and Peter Stenvinkel",

note = "Funding Information: This project has received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation programme under the Marie Sk{\l}odowska-Curie grant agreement No 722609 (INTRICARE). Peter Stenvinkels research was supported by grants provided by the Stockholm County Council,”Strategic Research Programme in Diabetes at Karolinska Institutet (Swedish Research Council grant No 2009-1068)”. Open access funding provided by Karolinska Institute. Funding Information: Dr. Schurgers reports consultancy fee from Immunodiagnostic systems (IDS), outside the submitted work and grants from NattoPharma outside the submitted work; Dr. Evenepoel reports personal fees from Vifor FMC, personal fees from Amgen, personal fees from Medice, grants from Sanofi outside the submitted work. Dr. Stenvinkel reports personal fees from Astellas, grants and personal fees from Astra Zeneca, personal fees from Reata, personal fees from Corvidia, personal fees from Baxter, personal fees from Pfizer, outside the submitted work. All other authors don{\textquoteright}t have competing interests. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = apr,

day = "20",

doi = "10.1038/s41598-020-63013-8",

language = "English",

volume = "10",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Matrix Gla protein is an independent predictor of both intimal and medial vascular calcification in chronic kidney disease

AU - Jaminon, Armand M. G.

AU - Dai, Lu

AU - Qureshi, Abdul Rashid

AU - Evenepoel, Pieter

AU - Ripsweden, Jonaz

AU - Soderberg, Magnus

AU - Witasp, Anna

AU - Olauson, Hannes

AU - Schurgers, Leon J.

AU - Stenvinkel, Peter

N1 - Funding Information: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 722609 (INTRICARE). Peter Stenvinkels research was supported by grants provided by the Stockholm County Council,”Strategic Research Programme in Diabetes at Karolinska Institutet (Swedish Research Council grant No 2009-1068)”. Open access funding provided by Karolinska Institute. Funding Information: Dr. Schurgers reports consultancy fee from Immunodiagnostic systems (IDS), outside the submitted work and grants from NattoPharma outside the submitted work; Dr. Evenepoel reports personal fees from Vifor FMC, personal fees from Amgen, personal fees from Medice, grants from Sanofi outside the submitted work. Dr. Stenvinkel reports personal fees from Astellas, grants and personal fees from Astra Zeneca, personal fees from Reata, personal fees from Corvidia, personal fees from Baxter, personal fees from Pfizer, outside the submitted work. All other authors don’t have competing interests. Publisher Copyright: © 2020, The Author(s).

PY - 2020/4/20

Y1 - 2020/4/20

N2 - 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.

AB - 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.

KW - STAGE RENAL-DISEASE

KW - CORONARY-ARTERY CALCIFICATION

KW - CARDIOVASCULAR EVENTS

KW - RISK

KW - SUPPLEMENTATION

KW - OSTEOCALCIN

KW - EXPRESSION

KW - MARKER

U2 - 10.1038/s41598-020-63013-8

DO - 10.1038/s41598-020-63013-8

M3 - Article

C2 - 32313061

SN - 2045-2322

VL - 10

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 6586

ER -