RESUMO
Matrix Gla Protein (MGP), a small Gla vitamin K-dependent protein, is the most powerful natural occurring inhibitor of calcification in the human body. To become biologically active, MGP must undergo vitamin K-dependent carboxylation and phosphorylation. Vitamin K deficiency leads to the inactive uncarboxylated, dephosphorylated form of MGP (dpucMGP). 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. Moreover, the association between vitamin K supplementation and serum levels of dpucMGP was also reviewed.
Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Doenças Cardiovasculares/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Processamento de Proteína Pós-Traducional , Insuficiência Renal Crônica/metabolismo , Calcificação Vascular/metabolismo , Deficiência de Vitamina K/metabolismo , Vitamina K/metabolismo , Transporte Biológico , Proteínas de Ligação ao Cálcio/genética , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/mortalidade , Suplementos Nutricionais , Proteínas da Matriz Extracelular/genética , Regulação da Expressão Gênica , Humanos , Fosforilação , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/mortalidade , Análise de Sobrevida , Calcificação Vascular/complicações , Calcificação Vascular/genética , Calcificação Vascular/mortalidade , Rigidez Vascular , Deficiência de Vitamina K/complicações , Deficiência de Vitamina K/genética , Deficiência de Vitamina K/mortalidade , Proteína de Matriz GlaRESUMO
Hereditary combined vitamin K-dependent clotting factors deficiency (VKCFD) is a rare congenital bleeding disorder resulting from variably decreased levels of coagulation factors II, VII, IX and X as well as natural anticoagulants protein C, protein S and protein Z. The spectrum of bleeding symptoms ranges from mild to severe with onset in the neonatal period in severe cases. The bleeding symptoms are often life-threatening, occur both spontaneously and in a surgical setting, and usually involve the skin and mucosae. A range of non-haemostatic symptoms are often present, including developmental and skeletal anomalies. VKCFD is an autosomal recessive disorder caused by mutations in the genes of either gamma-glutamyl carboxylase or vitamin K2,3-epoxide reductase complex. These two proteins are necessary for gamma-carboxylation, a post-synthetic modification that allows coagulation proteins to display their proper function. The developmental and skeletal anomalies seen in VKCFD are the result of defective gamma-carboxylation of a number of non-haemostatic proteins. Diagnostic differentiation from other conditions, both congenital and acquired, is mandatory and genotype analysis is needed to confirm the defect. Vitamin K administration is the mainstay of therapy in VKCFD, with plasma supplementation during surgery or severe bleeding episodes. In addition, prothrombin complex concentrates and combination therapy with recombinant activated FVII and vitamin K supplementation may constitute alternative treatment options. The overall prognosis is good and with the availability of several effective therapeutic options, VKCFD has only a small impact on the quality of life of affected patients.
Assuntos
Transtornos Herdados da Coagulação Sanguínea/fisiopatologia , Fatores de Coagulação Sanguínea/metabolismo , Proteínas Sanguíneas/metabolismo , Proteína C/metabolismo , Proteína S/metabolismo , Deficiência de Vitamina K/congênito , Transtornos Herdados da Coagulação Sanguínea/diagnóstico , Carbono-Carbono Ligases/genética , Carbono-Carbono Ligases/metabolismo , Humanos , Recém-Nascido , Proteínas Recombinantes/uso terapêutico , Vitamina K/uso terapêutico , Deficiência de Vitamina K/genéticaRESUMO
Vitamin K (K) is an essential factor for the posttranslational modification of blood coagulation factors as well as proteins in the bone matrix (Gla proteins). It is known that K is not only distributed in the liver and bones but also abundantly distributed in the brain, kidney, and gonadal tissues. However, the role of K in these tissues is not well clarified. In this study, we used DNA microarray and identified the genes whose expression was affected in the testis under the K-deficient (K-def) state. The expression of genes involved in the biosynthesis of cholesterol and steroid hormones was decreased in the K-def group. The mRNA levels of Cyp11a - a rate-limiting enzyme in testosterone synthesis - positively correlated with the menaquinone-4 (MK-4) concentration in the testis. Moreover, as compared to the control (Cont) and K-supplemented (K-sup) groups, the K-def group had decreased testosterone concentrations in the plasma and testis. These results suggested that K is involved in steroid production in the testis through the regulation of Cyp11a.
Assuntos
Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Testículo/metabolismo , Testosterona/biossíntese , Deficiência de Vitamina K/metabolismo , Alquil e Aril Transferases/genética , Animais , Carboxiliases/genética , Regulação para Baixo , Farnesiltranstransferase/genética , Hidroximetilglutaril-CoA Redutases/genética , Transferases Intramoleculares/genética , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Ratos , Vitamina K/metabolismo , Deficiência de Vitamina K/genéticaRESUMO
Congenital vitamin K-dependent coagulation factor deficiency is a very rare bleeding disorder, which usually presents with episodes of intracerebral bleed in the first few weeks of life, sometimes leading to a fatal outcome. We report a case of combined factor deficiency of vitamin K-dependent factors in which the patient presented with both intracerebral bleeding, and possibly also thrombosis, and responded to a vitamin K supplement along with fresh frozen plasma.
Assuntos
Deficiência de Vitamina K/congênito , Fatores de Coagulação Sanguínea/metabolismo , Consanguinidade , Hemorragia/etiologia , Humanos , Lactente , Trombose Intracraniana/sangue , Trombose Intracraniana/etiologia , Masculino , Deficiência de Vitamina K/sangue , Deficiência de Vitamina K/complicações , Deficiência de Vitamina K/genéticaRESUMO
Vitamin K is the cofactor for the hepatic carboxylation of glutamic acid residues in a number of proteins including the procoagulants factors II, VII, IX, and X. The role of vitamin K in normal bone function is not fully understood. Inherited deficiency of vitamin K dependent coagulation factors is a rare bleeding disorder reported only in a few patients. Here we present an 18-month old child who presented with osteopeni due to inherited vitamin K deficiency. While the patient had high bone specific alkaline phosphatase and parathyroid hormone levels and low osteocalcin and bone mineral density values, with the regular supplementation of vitamin K all the mentioned parameters returned to normal values.