Is Matrix Gla Protein Associated with Vascular Calcification? A Systematic Review

Barrett, Hilary E.; O’Keeffe, Mary; Kavanagh, Eamon G.; Walsh, Michael T.; O’Connor, Eibhlís M.

doi:10.3390/nu10040415

Cited by 70 publications

(62 citation statements)

References 63 publications

(122 reference statements)

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“…MGP is an essential calcification inhibitor and isolated from bone matrix and cartilage that requires vitamin K‐dependent γ‐carboxylation . Most previous studies have focused on the roles of MGP in cartilage, bone, and vessels, because vascular smooth muscle cells and chondrocytes are the major sites of MGP expression . Recently, studies indicated that MGP was deregulated in various types of cancer and the effects of MGP may be tumor type dependent.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of MGP by HOXC8 promotes the proliferation, migration, and EMT processes of triple‐negative breast cancer

Chen

Zhang

et al. 2019

Molecular Carcinogenesis

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Triple‐negative breast cancer (TNBC) is the most aggressive breast cancer subtype which accounts for 15%‐20% of all breast cancer cases. The management of TNBC has remained a challenge due to its lack of targeted therapy. Previously, we reported that homeobox C8 (HOXC8) was involved in metastasis and migration of breast cancer cells. By chromatin immunoprecipitation and luciferase assays, we found that HOXC8 functioned as a transcription factor to activate the transcription of matrix Gla protein (MGP) gene, leading to an increase in the proliferation, anchorage‐independent growth, and migration of TNBC cells. We further demonstrated that MGP expression promoted the epithelial‐mesenchymal transition (EMT) process of TNBC cells, but not the other subtypes of breast cancer, suggesting that MGP induced EMT to promote proliferation and migration of TNBC cells. Moreover, we found that MGP was upregulated in clinical breast specimens compared to normal breast tissues and high MGP expression was statistically associated with poor, relapse‐free survival for TNBC patients, indicating that MGP is probably a novel biomarker or therapeutic target for TNBC patients. Together, our results showed that the HOXC8‐MGP axis played an important role in the tumorigenesis of TNBC and might be a promising therapeutic target for TNBC treatment.

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Section: Discussionmentioning

confidence: 99%

Upregulation of MGP by HOXC8 promotes the proliferation, migration, and EMT processes of triple‐negative breast cancer

Chen

Zhang

et al. 2019

Molecular Carcinogenesis

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“…Diagnostic utility of MGP MGP is a 14 kDa vitamin K-dependent protein that is secreted mainly by vascular smooth muscle cells in the arterial medial layer and is a powerful inhibitor of vascular calcification [52]. MGP contains 5 gamma-carboxy- glutamic acid (Gla) residues, formed by post-translational modification of glutamic acid by gamma-glutamyl carboxylase, which requires active vitamin K (hydroquinone) as a coenzyme.…”

Section: Matrix Gla Proteinmentioning

confidence: 99%

Utility of Cardiac Biomarkers in the Setting of Kidney Disease

Savoj

Becerra

Kim

et al. 2019

Nephron

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Cardiovascular disease is prevalent in patients with chronic kidney disease (CKD) and responsible for approximately half of all CKD-related deaths. Unfortunately, the presence of CKD can lead to a challenging interpretation of cardiac biomarkers essential in accurate diagnosis and prompt management of heart failure and acute coronary syndrome. There is growing interest in novel cardiac biomarkers that may improve diagnostic accuracy reflecting myocardial injury, inflammation, and remodeling. Interpretation of these biomarkers in CKD can be complicated, since elevated levels may not reflect myocardial injury or wall tension but rather decreased urinary clearance with retention of solutes and/or overall CKD-associated chronic inflammation. In this review, we discuss the latest data on major and emerging cardiac biomarkers including B-type natriuretic peptide, troponin, suppression of tumorigenicity 2, growth and differentiation factor-15, galectin-3, and matrix gla protein, and their diagnostic and prognostic utility in the CKD population.

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“…However, to be active, MGP must be phosphorylated and carboxylated; such carboxylation is vitamin Kdependent, and phosphorylation is necessary for the secretion of MGP [2]. The vitamin K family includes phylloquinone (vitamin K1) and several menaquinones (vitamin K2) [2][3][4]. Notably, 72% of patients with chronic kidney disease (CKD) exhibit vitamin K intake lower than recommended levels [5].…”

Section: Introductionmentioning

confidence: 99%

Relationship of matrix Gla protein and vitamin K with vascular calcification in hemodialysis patients

Mizuiri¹,

Nishizawa²,

Yamashita³

et al. 2019

Renal Failure

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Objective: This study evaluated associations of serum matrix Gla protein (MGP), plasma vitamin K1, and plasma vitamin K2 with coronary artery calcium score (CACS) and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients. Methods: Subjects comprised 112 MHD patients aged 30-60 years and 40 age-matched healthy subjects. Total MGP, vitamin K1, vitamin K2, and lipid profile were examined in all subjects; other clinical data, medication use, and CACS were assessed only in MHD patients. Determinants of MGP in all subjects were identified by regression analysis. Factors associated with CACS and CVD in MHD patients were identified by regression analysis and logistic analysis, respectively. Results: Lower plasma levels of vitamin K1 corrected for triglycerides [0.39 (0.24-0.70) vs. 0.77 (0.48-1.34) ng/mg, p < 0.001], higher frequency of plasma vitamin K2 0.05 ng/ml (p ¼ 0.23), and higher serum total MGP (288.4 ± 44.2 vs. 159.7 ± 40.6 ng/ml, p < 0.0001) were observed in MHD patients than in healthy controls. Total MGP level was significantly associated with levels of vitamin K1 corrected for triglycerides (p <0 .001) and vitamin K2 0.05 ng/ml (p < 0.05) in all subjects. Total MGP level was significantly associated with presence of CVD (p <0 .05), but not CACS, in MHD patients. Conclusion: The end-stage renal disease on hemodialysis is a deficiency state of vitamin K. Total MGP was significantly higher in MHD patients compared to healthy subjects and total MGP was associated with the presence of CVD, but not CACS, in MHD patients.

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Is Matrix Gla Protein Associated with Vascular Calcification? A Systematic Review

Cited by 70 publications

References 63 publications

Upregulation of MGP by HOXC8 promotes the proliferation, migration, and EMT processes of triple‐negative breast cancer

Upregulation of MGP by HOXC8 promotes the proliferation, migration, and EMT processes of triple‐negative breast cancer

Utility of Cardiac Biomarkers in the Setting of Kidney Disease

Relationship of matrix Gla protein and vitamin K with vascular calcification in hemodialysis patients

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