ABSTRACT
No disponible
Subject(s)
Humans , Homocysteine/blood , Coronary Artery Disease/physiopathology , Coronary Disease/physiopathology , Biomarkers/blood , Folic Acid/bloodABSTRACT
Homocysteine is a methionine-derived amino acid and its metabolism depends on B12, B6 and B2 vitamins and folic acid. The total homocysteine plasmatic concentration can be measured in most laboratories by means of enzymeimmunoassays. Hyperhomocysteinemia may be caused by genetic defects of the enzymes involved in its metabolism, nutritional deficiencies or absorption deficiencies of the vitamin cofactors of these enzymes, chronic diseases or administration of some drugs. An increase in the total plasmatic concentration of homocysteine represents a sensitive marker of folate and cobalamin deficiencies as well as an independent risk factor of cardiovascular disease. Furthermore, total plasmatic concentrations of homocysteine are related to the development of congenital malformations, pregnancy complications, psychiatric diseases and to cognitive impairment in the elderly. Therefore, the measurement of the concentration of homocysteine has a notable clinical interest, which may increase in future if it is confirmed that the association with these disorders is causal and that they can be prevented by treating hyperhomocysteinemia.
Subject(s)
Folic Acid/metabolism , Homocysteine/blood , Hyperhomocysteinemia/physiopathology , Vitamin B 12/metabolism , Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Humans , Risk FactorsABSTRACT
La homocisteína es un aminoácido derivado de la metionina y su metabolismo depende de las vitaminas B12 (cobalamina), B6 (piridoxina),B2 (riboflavina) y ácido fólico. La concentración plasmática de homocisteína total puede ser medida en la mayoría de laboratorios mediante enzimoinmuno análisis. La hiperhomocisteinemia puede deberse a defectos genéticos en las enzimas que participan en el metabolismo de la homocisteína, deficiencias nutricionales o de absorción de los cofactores vitamínicos de estas enzimas, enfermedades crónicas o la ingesta de algunos fármacos. El aumento de la concentración plasmática de homocisteína total es un marcador sensible de las deficiencias de folato y cobalamina y un factor de riesgo independiente para la enfermedad cardiovascular. Además, las concentraciones plasmáticas de homocisteína total se relacionan con la aparición de malformaciones congénitas, complicaciones durante el embarazo, enfermedades psiquiátricas y con el deterioro cognitivo de los ancianos. Por todo ello, la medida de la concentración de homocisteína tiene un interés clínico notable, que podría aumentar en el futuro si se confirma quela asociación con estos procesos es causal y que el tratamiento de la hiperhomocisteinemia los previene
Homocysteine is a methionine-derived amino acid and its metabolism depends on B12, B6 and B2 vitamins and folic acid. The total homocysteine plasmatic concentration can be measured in most laboratories by means of enzymeimmuno assays. Hyperhomocysteinemia may be caused by genetic defects of the enzymes involved in its metabolism, nutritional deficiencies or absorption deficiencies of the vitaminco factors of these enzymes, chronic diseases or administration of some drugs. An increase in the total plasmatic concentration of homocysteinere presents a sensitive marker of folate and cobalamine deficiencies as well as an independent risk factor of cardiovascular disease. Furthermore, total plasmatic concentrations of homocysteine are related to the development of congenite malformations, pregnancy complications, psychiatric diseases and to cognitive impairment in the elderly. Therefore, the measurement of the concentration of homocysteine has a notable clinical interest, which may increase in future if it is confirmed that the association with these disorders is causal and that they can be prevented by treating hyperhomocysteinemia
Subject(s)
Humans , Homocysteine/blood , Hyperhomocysteinemia/physiopathology , Vitamin B 12/metabolism , Folic Acid/metabolism , Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Risk FactorsABSTRACT
INTRODUCTION AND OBJECTIVES: Systolic function and myocardial perfusion are evaluated before hospital discharge and can change during follow-up. The purpose of this study was to evaluate these parameters by gated-SPECT in the first year after acute myocardial infarction. PATIENTS AND METHOD: We studied 74 consecutive patients with a first uncomplicated acute myocardial infarction (49 infero-lateral and 25 anterior) by stress-rest 99mTc-tetrofosmin and rest-gated-SPECT before hospital discharge (6-8 days after admission) and one year after myocardial infarction. RESULTS: The ejection fraction (EF) increased > 5% in 51% of infero-lateral infarcts and 28% of non-revascularized anterior infarcts. EF increased significantly (48.4 8% to 54.6 8.7%; p < 0.0001, mean difference: 6.2; 95% IC, 2.8-9.5) and systolic volume decreased (51.3 19.2 ml to 44.3 19.4 ml; p = 0.001; mean diff.: 7.67; 95% IC, 1.5-13.8) in infero-lateral infarctions. The rest perfusion index in the necrotic region improved (2.3 0.57 to 2.17 0.58; p = 0.004; mean diff.: 0.18; 95% IC, 0.003-0.36) in infero-lateral infarcts and the ischemia index remained unchanged between the first and second studies. CONCLUSIONS: Left ventricular systolic function can change during the first year of evolution, a significant improvement being seen in infero-lateral infarctions. The ejection fraction increased > 5% in half of these patients, as opposed to only a quarter of anterior infarctions. This improvement was associated to increased myocardial perfusion at rest.
Subject(s)
Coronary Circulation/physiology , Heart/diagnostic imaging , Myocardial Infarction/physiopathology , Aged , Female , Humans , Male , Middle Aged , Stroke Volume/physiology , Tomography, Emission-Computed, Single-Photon , Ventricular Function, Left/physiologyABSTRACT
Introducción y objetivos. La función sistólica ventricular izquierda y la perfusión miocárdica pueden experimentar cambios durante el seguimiento y la evolución de un infarto agudo de miocardio. El objetivo de este estudio es su valoración mediante gated-SPECT. Pacientes y método. Se ha estudiado a 74 pacientes consecutivos con un primer infarto agudo de miocardio no complicado (49 inferolaterales y 25 anteriores) mediante 99m Tc-tetrofosmina de esfuerzo-reposo y gatedSPECT de reposo antes del alta hospitalaria y al año de evolución. Resultados. Entre el primer y el segundo estudios, la fracción de eyección aumentó > 5 por ciento en un 51 por ciento de los infartos inferolaterales y en un 28 por ciento de los infartos anteriores no revascularizados. El aumento de la FE (de 48,4 ñ 8 por ciento a 54,6 ñ 8,7 por ciento; p < 0,0001; diferencia media, 6,2; IC del 95 por ciento, 2,8-9,5) y el descenso del volumen sistólico (de 51,3 ñ 19,2 ml a 44,3 ñ 19,4 ml; p = 0,001; diferencia media, 7,67; IC del 95 por ciento, 1,5-13,8) alcanzaron valores estadísticamente significativos en los infartos inferolaterales. Los índices de perfusión en reposo en la región del infarto mejoraron entre los dos estudios en los infartos inferiores (de 2,3 ñ 0,57 a 2,17 ñ 0,58; p = 0,004; diferencia media, 0,18; IC del 95 por ciento, 0,003-0,36), sin cambios en los índices de isquemia. Conclusiones. La función sistólica ventricular izquierda puede cambiar durante el primer año de evolución, mejorando especialmente en los infartos inferolaterales. En la mitad de éstos, pero sólo en una cuarta parte de los anteriores, la fracción de eyección aumentó más de un 5 por ciento entre el primer y el segundo estudios. Esta mejoría se asoció a un incremento de la perfusión miocárdica en reposo (AU)
Subject(s)
Middle Aged , Aged , Male , Female , Humans , Stroke Volume , Tomography, Emission-Computed, Single-Photon , Ventricular Function, Left , Myocardial Infarction , Coronary Circulation , HeartABSTRACT
BACKGROUND: The regulatory molecule for cell life span, telomerase, was modified by human telomerase reverse transcriptase (hTERT) gene transfer to investigate its effect on regenerative properties of endothelial progenitor cells (EPCs) in neovascularization. METHODS AND RESULTS: Telomerase activity was enhanced in hTERT-transduced EPCs (Td-TERTs) (1.2-fold versus no transduced EPCs [no-Td] and 1.2-fold versus GFP-transduced EPCs [Td/GFPs] at day 8; 5.2-fold versus no-Td and 4.8-fold versus Td/GFP at day 21, respectively) Mitogenic capacity in Td/TERTs exceeded that in Td/GFPs at day 8 (0.62+/-0.02 versus 0.53+/-0.01, respectively; P<0.01). Vascular endothelial growth factor-induced cell migration in EPCs was markedly enhanced by hTERT overexpression (Td/TERTs versus Td/GFPs, 292+/-12 versus 174+/-6 cells, respectively; P<0.01). hTERT overexpression has rescued EPCs from starvation-induced cell apoptosis, an outcome that was further enhanced in response to vascular endothelial growth factor. The colony appearance of totally differentiated endothelial cells (tdECs) was detected before day 30 only in Td/TERT, whereas no tdEC colonies could be detected in both Td/GFPs and no-Tds. Finally, we investigated in vivo transplantation of heterologous EPCs. Td/TERTs dramatically improved postnatal neovascularization in terms of limb salvage by 4-fold in comparison with that of Td/GFPs; limb perfusion was measured by laser Doppler (0.77+/-0.10 versus 0.47+/-0.06; P=0.02), and capillary density (224+/-78 versus 90+/-40 capillaries/mm2; P<0.01). CONCLUSIONS: These findings provide the novel evidence that telomerase activity contributes to EPC angiogenic properties; mitogenic activity, migratory activity, and cell survival. This enhanced regenerative activity of EPCs by hTERT transfer will provide novel therapeutical strategy for postnatal neovascularization in severe ischemic disease patients.
Subject(s)
Endothelium, Vascular/metabolism , Regeneration , Stem Cells/metabolism , Telomerase/biosynthesis , Telomerase/metabolism , Adenoviridae/genetics , Animals , Apoptosis , Cell Differentiation , Cell Division , Cell Movement , Cells, Cultured , Cellular Senescence/physiology , DNA-Binding Proteins , Disease Models, Animal , Endothelium, Vascular/cytology , Enzyme Activation , Gene Expression , Hindlimb/blood supply , Hindlimb/physiopathology , Humans , Ischemia/physiopathology , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/metabolism , Mice , Mice, Nude , Regeneration/physiology , Reverse Transcriptase Polymerase Chain Reaction , Stem Cells/cytology , Telomerase/genetics , Transduction, Genetic , beta-Galactosidase/metabolismABSTRACT
Statins promote the proliferation, migration, and survival of endothelial cells and bone marrow-derived endothelial progenitor cells (angioblasts) by stimulating the serine/threonine protein kinase Akt (also known as protein kinase B) pathway. Like vascular endothelial growth factor (VEGF), the statins promote angiogenesis and vasculogenesis. Therefore, Akt activation may explain some of the beneficial effects of the statins, including postnatal neovascularization.
Subject(s)
Endothelium, Vascular/drug effects , Hypolipidemic Agents/pharmacology , Neovascularization, Physiologic/drug effects , Proto-Oncogene Proteins , Animals , Cells, Cultured , Cornea/drug effects , Corneal Neovascularization , Endothelial Growth Factors/physiology , Endothelium, Vascular/cytology , Humans , Intercellular Signaling Peptides and Proteins/physiology , Lymphokines/physiology , Mice , Protein Serine-Threonine Kinases/drug effects , Proto-Oncogene Proteins c-akt , RNA, Messenger/drug effects , Rabbits , Stem Cells/drug effects , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth FactorsABSTRACT
Las estatinas promueven la proliferación, migración y supervivencia celular de las células endoteliales y las células endoteliales progenitoras (angioblastos) procedentes de la médula ósea a través de mecanismos relacionados con la activación de la serina/treonina proteína cinasa Akt (o proteína cinasa B). De forma similar al factor de crecimiento endotelial vascular (VEGF), las estatinas promueven la angiogénesis y la vasculogénesis. Así pues, la activación de la Akt puede ser responsable de parte de los efectos beneficiosos de las estatinas, incluyendo la neovascularización posnatal (AU)
