Matrix Gla protein is associated with coronary artery calcification as assessed by electron-beam computed tomography

Abstract

Matrix Gla protein (MGP) is an extracellular matrix protein with wide tissue distribution. It has been demonstrated that the expression of MGP is detected not only in the normal blood vessels but also calcified atherosclerotic plaques, and that MGP deficient mice develop extensive arterial calcification. MGP is thought to be a regulator of vascular calcification. A recent clinical study demonstrates the association between polymorphisms of the MGP gene and increased risk of myocardial infarction. However, there are no reports of the relationship between serum MGP levels and coronary artery calcification (CAC). We evaluated the severity of CAC using electron-beam computed tomography (EBCT), and measured serum MGP levels by enzyme-linked immunosorbent assay in 115 subjects with suspected coronary artery disease. CAC scores were correlated with traditional risk factors, such as age, gender, hyper-tension, diabetes, hyperlipidemia and smoking. The serum MGP levels were lower in patients with CAC than in those without CAC (p<0.001). As the severity of CAC increased, there was a significant decrease in serum MGP levels. Serum MGP levels (U/L) were 116.7 +/- 20.3, 104.9 +/- 19.2, 95.2 +/- 15.2 and 82.2 +/- 19.7, (medians 115.5, 105.0, 94.8, and 81.9) for the subjects with normal (CAC score=0), mild (CAC score=1 to 99), moderate (CAC score=100 to 400), and severe (CAC score >400) coronary calcification, respectively. We found that serum MGP levels are inversely correlated with the severity of CAC. These data suggest a possible role for MGP in the development of vascular calcification.

Undercarboxylated matrix Gla protein is associated with indices of heart failure and mortality in symptomatic aortic stenosis

“…Numerous studies have confirmed that MGP is a calcification inhibitor, and alterations in circulating levels of MGP have been observed in different populations characterized by vascular calcification [13,[21][22][23]. In this study, we show markedly enhanced plasma levels of dp-cMGP and in particular of dp-ucMGP in patients with symptomatic AS.…”

Calcium scores and matrix Gla protein levels: association with vitamin K status

“…It provides the binding site of MGP to calcium. Reports on correlations between unphosphorylated MGP serum levels and coronary calcification scores have been conflicting [17,18,29]. Recently, ucMGP also failed to show a correlation with markers of vascular stiffness in children on dialysis [30].…”

“…On the contrary, the use of vitamin K antagonists is associated with increased coronary and cardiac valve calcification [15,16]. Studies on the relationship between coronary artery calcification and MGP gave conflicting results [17,18]. In this respect, vitamin K status may be of importance as studies with vascular smooth muscle cells have shown that MGP production is triggered by extra cellular calcium [19].…”

Coronary calcification in patients with end-stage renal disease: a novel endocrine disorder?

“…63 In patients with coronary heart disease and vascular wall calcifications, serum MGP levels were significantly reduced in comparison with patients without calcifications. 94 Vitamin K deficiency as a result of either malnutrition or systemic use of anticoagulants such as warfarin may possibly lead to vascular wall calcification. 88 Regardless of the mechanism involved, MGP constitutes an important inhibitor of vascular calcification and mineral precipitation, suggesting that it serves as a major vascular and bone homeostasis modulator.…”