Objective-Matrix ␥-carboxyglutamic acid (Gla) protein (MGP), a vitamin K-dependent protein, is a potent in vivo inhibitor of arterial calcification. We hypothesized that low endogenous production of MGP and impaired carboxylation of MGP may contribute to the development or the progression of vascular disease. Methods and Results-Novel conformation-specific antibodies against MGP were used for immunohistochemistry of healthy and sclerotic arteries. In healthy arteries, MGP was mainly displayed around the elastin fibers in the tunica media. The staining colocalized with that for carboxylated MGP, whereas undercarboxylated MGP (ucMGP) was not detected. In atherosclerotic arteries, ucMGP was found in the intima, where it was associated with vesicular structures. In Mönckeberg's sclerosis of the media, ucMGP was localized around all areas of calcification. The results indicate that ucMGP is strongly associated with vascular calcification of different etiologies. In a separate study, serum MGP concentrations in a cohort of 172 subjects who had undergone percutaneous coronary intervention were significantly reduced compared with an apparently healthy population. Key Words: matrix Gla protein (MGP) Ⅲ vitamin K Ⅲ calcification Ⅲ atherosclerosis T he extracellular fluids in the human body contain calcium and phosphate in high concentrations, even exceeding the solubility product for spontaneous precipitation. 1 However, physiological calcification is restricted to bone and teeth, whereas soft tissue calcification is regarded as pathological. Vascular calcification can occur at 3 anatomic sites: the intima where it is associated with atherosclerosis, the tunica media, and the heart valves. Huang et al showed that coronary artery calcification does not significantly affect stability of atheroma, 2 and the involvement of calcium salt accretion on cardiovascular disease is not known yet. However, overall vascular calcification is regarded as one of the major complications of cardiovascular disease and is an independent risk factor for myocardial infarction (MI) and cardiac death. [3][4][5][6] Therefore, prevention of vascular calcification is a prerequisite for human health. Inhibition of calcification is regarded presently as an active process in which a variety of proteins are involved throughout the body. 7 In the vasculature, a major calcification inhibitory factor is matrix ␥-carboxyglutamic acid (Gla) protein (MGP), a vitamin K-dependent protein synthesized by vascular smooth muscle cells (VSMCs). 8,9 Its 5 Gla residues are formed in a post-translational carboxylation reaction in which vitamin K functions as an essential cofactor. 10,11 MGP in its carboxylated form will be designated here as GlaMGP. The presence of the Gla residues is critical for MGP function, and undercarboxylated, inactive species of MGP (designated as GluMGP) are formed during inadequate vitamin K status or as a result of vitamin K antagonists. In animal models, it was demonstrated that impaired MGP synthesis 12,13 as well as treatment with vitamin ...
A behavioral intervention in PCI patients has a beneficial effect on feelings of exhaustion. It could not be demonstrated that the intervention reduces the risk of a new coronary event within 2 years.
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