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

Nutrients
Q1
Mar 2018
Citations:79
Influential Citations:3
Systematic Reviews / Meta-Analyses
83
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Enhanced Details

Methods
Systematic review of 28 studies including cross-sectional (n=23), longitudinal (n=2) and randomized controlled trials (n=3); participants included individuals with atherosclerosis, CKD (including children on dialysis), diabetes, and healthy controls; some studies involved Vitamin K supplementation, measured plasma Vitamin K, or Vitamin K antagonist usage.
Results
Findings show a multifaceted relationship between MGP fractions and vascular calcification that varies by arterial bed and disease state; no single MGP fraction consistently predicts calcification across conditions. In CKD, 6/10 studies reported significant correlations between MGP and calcification, while 4/10 reported non-significant results. In atherosclerosis, several studies showed correlations and ex vivo co-localization of non-functional MGP fractions with calcification. In diabetes, dp-ucMGP emerged as a positive risk factor for peripheral arterial calcification in one study, while t-ucMGP appeared protective in another. In healthy participants, four studies found no correlation, with one study suggesting an inverse relation for t-ucMGP. Vitamin K2 reduced dp-ucMGP but did not consistently slow progression of calcification; Vitamin K1 reduced progression in at least one trial. Overall, evidence is insufficient to guide clinical use; standardization of MGP assays, robust prospective multi-center trials, and consideration of dietary Vitamin K intake and confounders are needed to determine utility of MGP fractions as biomarkers and to clarify the impact of Vitamin K on vascular calcification.
Limitations
English-language restriction; potential publication bias; most studies cross-sectional, limiting causal inferences; risk of bias varied across studies; quality assessment used Cochrane criteria rather than a disease-specific tool; some full-text articles were not accessible, leading to exclusions; substantial heterogeneity in MGP assays and calcification outcomes; variation in imaging modalities and scoring; limited control for confounders in several studies.

Abstract

Specific patient cohorts are at increased risk of vascular calcification. Functional matrix-gla protein (MGP), a tissue-derived vitamin K dependent protein, is reported to be an important inhibitor of vascular calcification and may have clinical pote...