Gammacarboxyglutamic Acid Gla Proteins

Gla proteins, including matrix Gla protein (MGP) and osteocalcin (OC), are vitamin K-dependent bone proteins that play a key role as mediators and inhibitors of osteoid formation (Price et al., 1982; Pauli et al., 1987). MGP is a secretory protein that is widely expressed in tissues including bone and vasculature (Price et al., 1982). Chronic Warfarin therapy leads to depletion of these vitamin K-dependent Gla proteins, resulting in an excessive mineralization disorder and closure of the growth plate with cessation of longitudinal growth (Price et al., 1982). These features are similar to those observed in the warfarin embryopathy due to exposure of the human fetus to warfarin anticoagulation in early pregnancy (Pauli et al., 1987). Knockout mice lacking MGP develop to term but die within two months due to arterial calcification and blood-vessel rupture (Luo et al., 1997). Additionally, these MGP-deficient mice exhibit inappropriate calcification of the growth plate leading to short stature, osteopenia, and fractures (Luo et al., 1997). MGP are constitutively expressed in human aortas. These proteins are up-regulated in atherosclerosis and plaque formation (Shanahan et al., 2000), suggesting a role for these proteins in limiting vascular osteogenesis. MGP is expressed with high accumulation in bone and cartilage in association with bone morphogenetic protein (BMP) (Bostrom et al., 2001). MGP inhibits BMP-chondrocyte differentiation. Therefore, absence of MGP inhibitory effect leads to osteogenic differentiation and vascular calcification (Bostrom et al., 2001). However, MGP was suggested to prevent nucleation and growth of crystals via binding to hydroxyapatite (Schnike et al., 1999). These two mechanisms are likely operative in prevention of vascular calcification.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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