Furthermore, since warfarin inhibits the vitamin K-dependent gamma-glutamyl carboxylation of proteins, including osteocalcin and matrix Gla protein, use of warfarin may increase the risk of osteoporotic bone fracture and vascular calcification, both of which are the leading causes of morbidity that diminish the quality of life in diabetic patients.
Vascular calcification (VC) is an independent risk factor for cardiovascular disease in hemodialysis patients while Matrix GLA protein (MGP) is one of the most potent inhibitors of VC and its activation is vitamin K dependent.
Vitamin K supplementation was associated with significant reduction in VC (-9.1% (95% CI -17.7 to -0.5); p=0.04) and VKDP (desphospho-uncarboxylated matrix Gla protein; -44.7% (95% CI -65.1 to -24.3), p<0.0001) and uncarboxylated osteocalcin; -12.0% (95% CI -16.7 to -7.2), p<0.0001) compared with control, with a non-significant improvement in VS.
Vascular and valvular calcification associated with warfarin could result from reduced carboxylation of matrix Gla protein (MGP), a well-known inhibitor of vascular calcification.
In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival.
We aimed to review the existing data on the association between circulating dpucMGP and vascular calcification, renal function, mortality, and cardiovascular disease in distinct populations.
As a consequence of this finding, the present study was undertaken to investigate if inducers and inhibitors of VC (i.e. the inactive matrix Gla protein fractions dp-ucMGP and t-ucMGP, fetuin-A, Gla-rich protein (GRP), osteopontin (OPN), bone-specific alkaline phosphatase (BALP), and osteoprotegerin (OPG)) also are affected by ol-HDF.
This systematic review examines twenty-eight studies which assess the relationship between circulating protein expressions of MGP species and vascular calcification in different arterial beds.
The expression of the MGP gene can be regulated via various mechanisms that have the potential to become genomic biomarkers for the prediction of vascular calcification (VC) progression.
Calcitriol [1,25-(OH)<sub>2</sub>-D<sub>3</sub>] is a key transcriptional regulator of matrix Gla protein, a vitamin K-dependent protein that inhibits vascular calcification.
Association of Matrix Gla protein gene (rs1800801, rs1800802, rs4236) polymorphism with vascular calcification and atherosclerotic disease: a meta-analysis.
All these findings were also functionally corroborated in two vascular and bone in vitro systems indicating that MGP genetic variations can be partly responsible of higher risk of bone loss and vascular calcification.