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Am J Hypertens. 2017 Feb;30(2):196-201. doi: 10.1093/ajh/hpw146. Epub 2016 Dec 7.

Inactive Matrix Gla-Protein and Arterial Stiffness in Type 2 Diabetes Mellitus.

Author information

1
Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
2
Department of Medicine, Corporal Michael J. Crescenz VA MC, Philadelphia, Pennsylvania, USA.
3
Cardiology Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine and Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
4
R&D Group, VitaK, Maastricht University, Maastricht, The Netherlands.
5
Department of Medicine, Corporal Michael J. Crescenz VA MC, Philadelphia, Pennsylvania, USA; Julio.chirinos@uphs.upenn.edu.

Abstract

BACKGROUND:

Large artery stiffness is increased in diabetes mellitus and causes an excessive pulsatile load to the heart and to the microvasculature. The identification of pathways related to arterial stiffness may provide novel therapeutic targets to ameliorate arterial stiffness in diabetes. Matrix Gla-Protein (MGP) is an inhibitor of vascular calcification. Activation of MGP is vitamin K dependent. We hypothesized that levels of inactive MGP (dephospho-uncarboxylated MGP; dp-ucMGP) are related to arterial stiffness in type 2 diabetes.

METHODS:

We enrolled a multiethnic cohort of 66 participants with type 2 diabetes. Carotid-femoral pulse wave velocity (CF-PWV) was measured with high-fidelity arterial tonometry (Sphygmocor Device). Dp-ucMGP was measured with ELISA (VitaK; The Netherlands).

RESULTS:

The majority of the participants were middle-aged (62 ± 12 years), male (91%), and had a history of hypertension (82%). Average hemoglobin A1C was 7.2% (55 mmol/mol). Mean dp-ucMGP was 624 ± 638 pmol/l and mean CF-PWV was 11 ± 4 m/sec. In multivariable analyses, dp-ucMGP was independently related to African American ethnicity (β = -0.24, P = 0.005), warfarin use (β = 0.56, P < 0.001), and estimated glomerular filtration rate (eGFR, β = -0.32, P < 0.001). Dp-ucMGP predicted CF-PWV (β = 0.40, P = 0.011), even after adjustment for age, gender, ethnicity, mean arterial pressure, eGFR, and warfarin use.

CONCLUSIONS:

In our cross-sectional analysis, circulating dp-ucMGP was independently associated with CF-PWV in type 2 diabetes. This suggests that deficient vitamin K-dependent activation of MGP may lead to large artery stiffening and could be targeted with vitamin K supplementation in the patients with diabetes.

KEYWORDS:

Matrix Gla-Protein; arterial stiffness; blood pressure; diabetes mellitus; hypertension; pulse wave velocity; vitamin K.

PMID:
27927630
DOI:
10.1093/ajh/hpw146
[Indexed for MEDLINE]

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