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1.
Eur J Appl Physiol ; 113(5): 1249-55, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23160657

RESUMEN

Matrix metalloproteinase 9 (MMP-9) is a member of a family of zinc-dependent endopeptidases capable of degrading extracellular matrix (ECM) proteins. A single bout of exercise increases levels of activated MMP-9 in skeletal muscle and in the circulation. However, whether the exercise-induced activation of MMP-9 is associated with ECM remodeling and the cellular source behind MMP-9 in the circulation is not known. In the present study ten healthy male subjects performed a single cycle exercise bout and arterial and venous femoral blood was collected. To test if exercise induces basal lamina degradation and if circulating levels of MMP-9 is related to a release from the exercising muscle, arteriovenous differences of collagen IV and MMP-9 were measured by ELISA and zymography, respectively. Furthermore, markers of neutrophil degranulation elastase and neutrophil gelatinase-associated lipocalin (NGAL) were measured by ELISA. Plasma levels of collagen IV increased during the exercise bout and an increased arteriovenous difference of collagen IV was noted at 27 min of exercise. Plasma levels of MMP-9 were increased at both 27 and 57 min of exercise but no arteriovenous difference was noted. No changes over time were detected for elastase and NGAL. The observed release of collagen IV from the exercising muscle indicate basal lamina turnover following a single bout of exercise. No detectable release of MMP-9 was observed, suggesting that the increase in plasma MMP-9 could come from a source other than the skeletal muscle.


Asunto(s)
Ejercicio Físico , Metaloproteinasa 9 de la Matriz/sangre , Proteínas de Fase Aguda , Adolescente , Adulto , Membrana Basal/enzimología , Membrana Basal/metabolismo , Colágeno Tipo IV/sangre , Endotelio Vascular/enzimología , Endotelio Vascular/metabolismo , Matriz Extracelular/metabolismo , Humanos , Elastasa de Leucocito/sangre , Lipocalina 2 , Lipocalinas/sangre , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Músculo Esquelético/enzimología , Músculo Esquelético/metabolismo , Neutrófilos/enzimología , Proteínas Proto-Oncogénicas/sangre
2.
J Intern Med ; 270(3): 229-36, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21332844

RESUMEN

OBJECTIVES: A common nonsynonymous single nucleotide polymorphism (SNP) in the CD93 gene (rs3746731, Pro541Ser) has been associated with risk of coronary artery disease (CAD). CD93 is a transmembrane glycoprotein, which is detectable in soluble form in human plasma. We investigated whether the concentration of soluble CD93 in plasma is related to risk of myocardial infarction (MI) and CAD, using a case-control study of premature MI (n = 764) and a nested case-control analysis of a longitudinal cohort study of 60-year-old subjects (analysis comprising 844 of 4232 subjects enrolled at baseline). In addition, SNPs in the CD93 gene were studied in relation to plasma CD93 concentration and CD93 mRNA expression. METHODS AND RESULTS: A sensitive and specific enzyme-linked immunosorbent assay was established for determination of the plasma CD93 concentration. Subjects were divided into three groups according to tertiles of the distribution of CD93 concentration. Lower odds ratios for risk of MI and incidence of CAD were observed in the middle CD93 tertile (142-173 µg L(-1) ): odds ratio (95% confidence interval), 0.69 (0.49-0.97) and 0.61 (0.40-0.94), respectively. These associations were independent of traditional CAD risk factors. The minor allele of a SNP in the 3' untranslated region of CD93 (rs2749812) was associated with increased plasma CD93 concentrations (P = 0.03) and increased CD93 mRNA expression levels (P = 0.02). CONCLUSION: The results of the present study suggest that the concentration of soluble CD93 in plasma is a potential novel biomarker for CAD, including MI.


Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Glicoproteínas de Membrana/sangre , Glicoproteínas de Membrana/genética , Polimorfismo de Nucleótido Simple , Receptores de Complemento/sangre , Receptores de Complemento/genética , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/genética , Oportunidad Relativa , Valor Predictivo de las Pruebas , Prolina , Estudios Prospectivos , ARN Mensajero/sangre , Medición de Riesgo , Factores de Riesgo , Serina
3.
J Infect Dis ; 200(2): 252-62, 2009 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-19519254

RESUMEN

BACKGROUND: Long-term use of both zidovudine (AZT) and stavudine (d4T) is associated with lipoatrophy, but it occurs possibly through different mechanisms. METHODS: Surgical biopsy specimens of subcutaneous adipose tissue were obtained from 18 human immunodeficiency virus type 1 (HIV-1)-infected lipoatrophic patients (the LA+ group) who were treated with either zidovudine (the AZT+LA+ group; n = 10) or stavudine (the d4T+LA+ group; n = 8) and from 10 nonlipoatrophic HIV-1-infected patients (the LA- group) who received antiretroviral therapy. Mitochondrial DNA (mtDNA) copy numbers, gene expression, and immunohistochemistry data were analyzed. RESULTS: mtDNA copy numbers were significantly reduced in the LA+ group, compared with the LA- group, and in the d4T+LA+ group, compared with the AZT+LA+ group. The ratio of mtDNA-encoded cytochrome COX3 to nuclear DNA-encoded COX4 expression was significantly lower in the LA+ group than in the LA- group. Compared with the LA- group, the LA+ group had significantly lower expression of genes involved in adipogenesis (SREBP1c and CEBPB), lipid (fatty acid synthase), and glucose (GLUT4) metabolism. Expression of genes involved in mitochondrial biogenesis (PGC1B), apoptosis (FAS), inflammation (IL1B), oxidative stress (PCNA and SOD1), and lamin B was significantly higher in the LA+ group than in the LA- group. The d4T+LA+ group had significantly lower expression of genes involved in mitochondrial biogenesis (POLG1), energy metabolism (the COX3/COX4 ratio), adipogenesis (SREBP1c and CEBPA), perilipin, and hexokinase than did the AZT+LA+ group. There were 7-fold more macrophages in adipose tissue specimens obtained from patients in the LA+ group, compared with the LA- group. CONCLUSIONS: Lipoatrophy is characterized by mtDNA depletion, inflammation, and signs of apoptosis. Changes were more profound in the d4T+LA+ group than in the AZT+LA+ group.


Asunto(s)
Fármacos Anti-VIH/efectos adversos , VIH-1 , Síndrome de Lipodistrofia Asociada a VIH/metabolismo , Inhibidores de la Transcriptasa Inversa/efectos adversos , Estavudina/efectos adversos , Zidovudina/efectos adversos , Adipocitos/metabolismo , Fármacos Anti-VIH/uso terapéutico , ADN Polimerasa gamma , ADN Mitocondrial/efectos de los fármacos , ADN Mitocondrial/metabolismo , ADN Polimerasa Dirigida por ADN , Femenino , Perfilación de la Expresión Génica , Regulación Viral de la Expresión Génica/efectos de los fármacos , Glucosa/metabolismo , VIH-1/efectos de los fármacos , VIH-1/genética , Síndrome de Lipodistrofia Asociada a VIH/inducido químicamente , Síndrome de Lipodistrofia Asociada a VIH/tratamiento farmacológico , Humanos , Inmunohistoquímica , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Inhibidores de la Síntesis del Ácido Nucleico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Estavudina/uso terapéutico , Grasa Subcutánea Abdominal/metabolismo , Grasa Subcutánea Abdominal/patología , Zidovudina/uso terapéutico
4.
J Appl Physiol (1985) ; 102(6): 2346-51, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17255365

RESUMEN

The aims of this study were 1) to characterize changes in matrix metalloproteinase (MMP), endostatin, and vascular endothelial growth factor (VEGF)-A expression in skeletal muscle in response to a single bout of exercise in humans; and 2) to determine if any exchange of endostatin and VEGF-A between circulation and the exercising leg is associated with a change in the tissue expression or plasma concentration of these factors. Ten healthy males performed 65 min of cycle exercise, and muscle biopsies were obtained from the vastus lateralis muscle at rest and immediately and 120 min after exercise. In the muscle biopsies, measurements of mRNA expression levels of MMP-2, MMP-9, MMP-14, and tissue inhibitor of metalloproteinase; VEGF and endostatin protein levels; and MMP activities were performed. Femoral arterial and venous concentrations of VEGF-A and endostatin were determined before, during, and 120 min after exercise. A single bout of exercise increased MMP-9 mRNA and activated MMP-9 protein in skeletal muscle. No measurable increase of endostatin was observed in the skeletal muscle or in plasma following exercise. A concurrent increase in skeletal muscle VEGF-A mRNA and protein levels was induced by exercise, with no signs of peripheral uptake from the circulation. However, a decrease in plasma VEGF-A concentration occurred following exercise. Thus 1) a single bout of exercise activated the MMP system without any resulting change in tissue endostatin protein levels, and 2) the increased VEGF-A protein levels are due to changes in the skeletal muscle tissue itself. Other mechanisms are responsible for the observed exercise-induced decrease in VEGF-A in plasma.


Asunto(s)
Envejecimiento/fisiología , Metaloproteinasas de la Matriz/metabolismo , Contracción Muscular/fisiología , Músculo Esquelético/fisiología , Esfuerzo Físico/fisiología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Endostatinas/metabolismo , Activación Enzimática , Prueba de Esfuerzo , Humanos , Masculino , Persona de Mediana Edad
5.
Arterioscler Thromb Vasc Biol ; 25(7): e113-6, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15890971

RESUMEN

OBJECTIVE: Inflammatory processes play an important role in atherosclerosis, and increasing evidence implies that microbial pathogens and proinflammatory cytokines are involved in the development and activation of atherosclerotic lesions. To find new inflammatory genes, we explored the vascular transcriptional response to an activator of innate immunity bacterial lipopolysaccharides (LPSs). METHODS AND RESULTS: Gene arrays identified the cytomegalovirus-inducible gene 5 (cig5)/viperin among the genes most potently induced by LPS in human vascular biopsies. Viperin was expressed by endothelial cells in atherosclerotic arteries and significantly elevated in atherosclerotic compared with normal arteries. In culture, cytomegalovirus infection, interferon-gamma, and LPS induced viperin expression. CONCLUSIONS: Viperin is expressed in atherosclerosis and induced in vascular cells by inflammatory stimuli and cytomegalovirus infection. The putative functions of viperin in atherosclerosis may relate to disease-associated microbes.


Asunto(s)
Enfermedades de las Arterias Carótidas/fisiopatología , Infecciones por Citomegalovirus/fisiopatología , Citomegalovirus/genética , Proteínas/genética , Vasculitis/fisiopatología , Animales , Apolipoproteínas E/genética , Biopsia , Arterias Carótidas/patología , Enfermedades de las Arterias Carótidas/inmunología , Enfermedades de las Arterias Carótidas/patología , Células Cultivadas , Vasos Coronarios/citología , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/patología , Endotelio Vascular/citología , Expresión Génica/efectos de los fármacos , Expresión Génica/inmunología , Humanos , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Músculo Liso Vascular/citología , Análisis de Secuencia por Matrices de Oligonucleótidos , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH , Arteria Renal/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Venas Umbilicales/citología , Vasculitis/inmunología , Vasculitis/patología
6.
J Exp Clin Cancer Res ; 22(3): 471-5, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-14582708

RESUMEN

Accumulated evidence supports that both Id helix-loop-helix proteins and derivatives of vitamin A, retinoids, play a pivotal role in the regulation of cell growth and differentiation. We analyzed the effects of all-trans retinoic acid (atRA) on the gene and protein expression of Id2 in THP-1 cells and found a suppression of the levels of Id2. The down-regulation was abolished towards a constitutively expressed level of Id2 mRNA. The decreased level of Id2 was associated with growth suppression and does support the prevalent conception of the action of Id2 as a stimulator of cell growth.


Asunto(s)
Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Proteínas Represoras , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Tretinoina/farmacología , Diferenciación Celular , Línea Celular Tumoral , Humanos , Proteína 2 Inhibidora de la Diferenciación , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Tiempo
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