RESUMEN
Matrix γ-carboxyglutamate (Gla) protein (MGP) is an important local inhibitor of vascular calcification, which can undergo two post-translational modifications: vitamin K-dependent γ-glutamate carboxylation and serine phosphorylation. While carboxylation is thought to have effects upon binding of calcium-ions, phosphorylation is supposed to affect the cellular release of MGP. Since both modifications can be exerted incompletely, various MGP species can be detected in the circulation. MGP levels were measured with two commercially available competitive and two novel sandwich assays in healthy controls, in patients with rheumatic disease, aortic valve disease, and end-stage renal disease, as well as in volunteers after vitamin K supplementation (VKS) and treatment with vitamin K antagonists (VKA). Major differences were found between the MGP assays, including significantly different behaviour with regard to vascular disease and the response to VKA and VKS. The dual-antibody assay measuring non-phosphorylated, non-carboxylated MGP (dp-ucMGP) was particularly sensitive for these changes and would be suited to assess the vascular vitamin K status. We conclude that the different assays for particular circulating MGP species allows the assessment of various aspects of the MGP system.
Asunto(s)
Insuficiencia de la Válvula Aórtica/diagnóstico , Artritis Reumatoide/diagnóstico , Proteínas de Unión al Calcio/biosíntesis , Condrocalcinosis/diagnóstico , Proteínas de la Matriz Extracelular/biosíntesis , Fallo Renal Crónico/diagnóstico , Adulto , Anciano , Anticuerpos Monoclonales/metabolismo , Insuficiencia de la Válvula Aórtica/sangre , Insuficiencia de la Válvula Aórtica/fisiopatología , Artritis Reumatoide/sangre , Artritis Reumatoide/fisiopatología , Biomarcadores/sangre , Calcinosis , Proteínas de Unión al Calcio/sangre , Proteínas de Unión al Calcio/genética , Condrocalcinosis/sangre , Condrocalcinosis/fisiopatología , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática/métodos , Proteínas de la Matriz Extracelular/sangre , Proteínas de la Matriz Extracelular/genética , Estudios de Factibilidad , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/fisiopatología , Persona de Mediana Edad , Pronóstico , Procesamiento Proteico-Postraduccional , Vitamina K/administración & dosificación , Vitamina K/sangre , Proteína Gla de la MatrizRESUMEN
Phosphorus-31 magnetic resonance spectroscopy can be used to study intracellular biochemistry non-invasively by measuring the relative proportions of high energy phosphates. Study of deteriorating cardiac metabolism might be useful in the management of hypertrophy and heart failure. 31P magnetic resonance spectroscopy was carried out in fourteen patients with aortic valve disease (six with aortic stenosis, eight with aortic incompetence). Six patients were receiving treatment for symptoms of heart failure. The phosphocreatine (PCr) to ATP ratio in these patients (1.1 [SD 0.32]) was significantly lower than that in thirteen controls (1.5 [0.2], p less than 0.001) or in the eight patients who did not have symptoms of heart failure (1.56 [0.15], p less than 0.0035). These findings indicate that heart failure in aortic valve disease is associated with low PCr, which could be due to loss of intracellular creatine. The measurement could eventually have a role in helping to determine the optimum timing for aortic valve replacement.