Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Rev Med Suisse ; 16(680): 296, 2020 Feb 05.
Artigo em Francês | MEDLINE | ID: mdl-32022502
6.
Rev Med Suisse ; 14(625): 1972, 2018 Oct 31.
Artigo em Francês | MEDLINE | ID: mdl-30379486
7.
Rev Med Suisse ; 14(625): 1973, 2018 Oct 31.
Artigo em Francês | MEDLINE | ID: mdl-30379487
10.
Rev Med Suisse ; 14(590): 155, 2018 Jan 17.
Artigo em Francês | MEDLINE | ID: mdl-29341530
11.
Rev Med Suisse ; 14(590): 156, 2018 Jan 17.
Artigo em Francês | MEDLINE | ID: mdl-29341531
12.
Rev Med Suisse ; 14(590): 157, 2018 Jan 17.
Artigo em Francês | MEDLINE | ID: mdl-29341532
14.
J Mol Cell Cardiol ; 56: 106-15, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23277190

RESUMO

Cardiotrophin-1 (CT-1) is a heart-targeting cytokine that is increased in the metabolic syndrome due to overexpression in the adipocytes. The effects of CT-1 on cardiomyocyte substrate metabolism remain unknown. We therefore determined the effects of CT-1 on basal and stimulated glucose transport in cardiomyocytes exposed to a low dose (1nM) or a high dose (10nM). Dose-response curves for insulin showed that 1nM CT-1 reduced insulin responsiveness, while 10nM CT-1 increased insulin responsiveness. In either condition insulin sensitivity was unaffected. Similarly 1nM CT-1 reduced the stimulation of glucose transport in response to metabolic stress, induced by the mitochondrial poison oligomycin, while 10nM CT-1 increased this response. Reduction of stimulated glucose transport by 1nM CT-1 was associated with overexpression of SOCS-3, a protein known to hinder proximal insulin signaling, and increased phosphorylation of STAT5. In cardiomyocytes exposed to 1nM CT-1 there was also reduced phosphorylation of Akt and AS160 in response to insulin, and of AMPK in response to oligomycin. Insulin-stimulated glucose transport and signaling were restored by inhibition of STAT5 activity. On the other hand in cardiomyocytes exposed to 10nM CT-1 there was increased phosphorylation of the AS160 and Akt in response to insulin. Most importantly, basal and oligomycin-stimulated phosphorylation of AMPK was markedly increased in cardiomyocytes exposed to 10nM CT-1. The enhancement of basal and stimulated-glucose transport was abolished in cardiomyocytes treated with the calmodulin-dependent kinase II (CaMKII) inhibitor KN93, and so was AMPK phosphorylation. This suggests that activation of CaMKII mediates activation of AMPK by a high dose of CT-1 independently of metabolic stress. Our results point to a role for CT-1 in the regulation of myocardial glucose metabolism and implicate entirely separate mechanisms in the inhibitory or stimulatory effects of CT-1 on glucose transport at low or high concentrations respectively.


Assuntos
Citocinas/fisiologia , Glucose/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Transporte Biológico , Hipóxia Celular , Células Cultivadas , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Insulina/fisiologia , Masculino , Oligomicinas/farmacologia , Fosforilação , Processamento de Proteína Pós-Traducional , Piruvato Desidrogenase (Lipoamida)/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT5/antagonistas & inibidores , Fator de Transcrição STAT5/metabolismo , Transdução de Sinais , Estresse Fisiológico
15.
Stem Cells Transl Med ; 1(3): 248-60, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23197784

RESUMO

Pluripotent stem cell-seeded cardiopatches hold promise for in situ regeneration of infarcted hearts. Here, we describe a novel cardiopatch based on bone morphogenetic protein 2-primed cardiac-committed mouse embryonic stem cells, embedded into biodegradable fibrin matrices and engrafted onto infarcted rat hearts. For in vivo tracking of the engrafted cardiac-committed cells, superparamagnetic iron oxide nanoparticles were magnetofected into the cells, thus enabling detection and functional evaluation by high-resolution magnetic resonance imaging. Six weeks after transplantation into infarcted rat hearts, both local (p < .04) and global (p < .015) heart function, as well as the left ventricular dilation (p < .0011), were significantly improved (p < .001) as compared with hearts receiving cardiopatches loaded with iron nanoparticles alone. Histological analysis revealed that the fibrin scaffolds had degraded over time and clusters of myocyte enhancer factor 2-positive cardiac-committed cells had colonized most of the infarcted myocardium, including the fibrotic area. De novo CD31-positive blood vessels were formed in the vicinity of the transplanted cardiopatch. Altogether, our data provide evidence that stem cell-based cardiopatches represent a promising therapeutic strategy to achieve efficient cell implantation and improved global and regional cardiac function after myocardial infarction.


Assuntos
Diferenciação Celular , Células-Tronco Embrionárias/citologia , Coração/fisiologia , Infarto do Miocárdio/terapia , Transplante de Células-Tronco , Animais , Células-Tronco Embrionárias/fisiologia , Técnicas Imunoenzimáticas , Imagem por Ressonância Magnética , Masculino , Camundongos , Ratos
16.
NMR Biomed ; 25(4): 489-97, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21796712

RESUMO

Manganese (Mn(2+)) is considered as a specific MRI contrast agent that enters viable cardiomyocytes through calcium pathways. Compared to extracellular gadolinium based contrast agents, it has the potential to assess cell viability. To date, only information from the washout phase after recirculation has been used for the detection and characterization of myocardial infarct. This study showed for the first time that in a mouse model of coronary occlusion-reperfusion, Mn(2+) wash-in kinetics are different at 24 h after surgery (acute infarction) than at eight days after surgery (chronic infarction). A fast but transient entry of Mn(2+) into the acute infarct area led to a double contrast between infarct and remote areas, whereas entry of Mn(2+) into the chronic infarct area remained reduced compared to remote regions during both wash-in and washout phases. The main hypothesis is that extracellular space is largely enhanced in acute infarction due to cell membrane rupture and interstitial edema, whereas scar tissue is densely composed of collagen fibers that reduce the distribution volume of free Mn(2+) ions. In addition to its ability to accurately depict the infarct area during the redistribution phase, Mn(2+) is also able to discriminate acute versus chronic injury by the observation of double-contrast kinetics in a mouse model of ischemia reperfusion.


Assuntos
Modelos Animais de Doenças , Imagem por Ressonância Magnética/métodos , Manganês/farmacocinética , Traumatismo por Reperfusão Miocárdica/diagnóstico , Traumatismo por Reperfusão Miocárdica/metabolismo , Doença Aguda , Animais , Doença Crônica , Meios de Contraste/farmacocinética , Humanos , Cinética , Espectroscopia de Ressonância Magnética/métodos , Taxa de Depuração Metabólica , Camundongos , Camundongos Endogâmicos C57BL , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
17.
Mol Cell Biochem ; 340(1-2): 239-47, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20306288

RESUMO

We have previously reported in the early septating embryonic heart that electromechanical disturbances induced by anoxia-reoxygenation are distinct in atria, ventricle, and outflow tract, and are attenuated in ventricle by opening of mitochondrial K(ATP) (mitoK(ATP)) channels. Here, we assessed the regional activation of mitogen-activated protein kinases (MAPKs) ERK, p38, and JNK in response to anoxia-reoxygenation and H(2)O(2). Hearts isolated from 4-day-old chick embryos were subjected to 30-min anoxia and 60-min reoxygenation or exposed to H(2)O(2) (50 microM-1 mM). The temporal pattern of activation of ERK, p38, and JNK in atria, ventricle, and outflow tract was determined using immunoblotting and/or kinase assay. The effect of the mitoK(ATP) channel opener diazoxide (50 microM) on JNK phosphorylation was also analyzed. Under basal conditions, total ERK and JNK were homogeneously distributed within the heart, whereas total p38 was the lowest in outflow tract. The phosphorylated/total form ratio of each MAPK was similar in all regions. Phosphorylation of ERK increased in atria and ventricle at the end of reoxygenation without change in outflow tract. Phosphorylation of p38 was augmented by anoxia in the three regions, and returned to basal level at the end of reoxygenation except in the outflow tract. JNK activity was not altered by anoxia-reoxygenation in atria and outflow tract. In ventricle, however, the diazoxide-inhibitable peak of JNK activity known to occur during reoxygenation was not accompanied by a change in phosphorylation level. H(2)O(2) over 500 microM impaired cardiac function, phosphorylated ERK in all the regions and p38 in atria and outflow tract, but did not affect JNK phosphorylation. At a critical stage of early cardiogenesis, anoxia, reoxygenation, exogenous H(2)O(2) and opening of mitoK(ATP) channels can subtly modulate ERK, p38, and JNK pathways in a region-specific manner.


Assuntos
Coração/embriologia , Peróxido de Hidrogênio/farmacologia , Hipóxia/enzimologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Miocárdio/enzimologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Embrião de Galinha , Diazóxido/farmacologia , Relação Dose-Resposta a Droga , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Coração/efeitos dos fármacos , Hipóxia/embriologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fosforilação , Canais de Potássio/agonistas , Canais de Potássio/metabolismo , Fatores de Tempo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
Pharmacol Res ; 61(1): 85-91, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19818405

RESUMO

The hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are expressed in pacemaker cells very early during cardiogenesis. This work aimed at determining to what extent these channels are implicated in the electromechanical disturbances induced by a transient oxygen lack which may occur in utero. Spontaneously beating hearts or isolated ventricles and outflow tracts dissected from 4-day-old chick embryos were exposed to a selective inhibitor of HCN channels (ivabradine 0.1-10microM) to establish a dose-response relationship. The effects of ivabradine on electrocardiogram, excitation-contraction coupling and contractility of hearts submitted to anoxia (30min) and reoxygenation (60min) were also determined. The distribution of the predominant channel isoform, HCN4, was established in atria, ventricle and outflow tract by immunoblotting. Intrinsic beating rate of atria, ventricle and outflow tract was 164+/-22 (n=10), 78+/-24 (n=8) and 40+/-12bpm (n=23, mean+/-SD), respectively. In the whole heart, ivabradine (0.3microM) slowed the firing rate of atria by 16% and stabilized PR interval. These effects persisted throughout anoxia-reoxygenation, whereas the variations of QT duration, excitation-contraction coupling and contractility, as well as the types and duration of arrhythmias were not altered. Ivabradine (10microM) reduced the intrinsic rate of atria and isolated ventricle by 27% and 52%, respectively, whereas it abolished activity of the isolated outflow tract. Protein expression of HCN4 channels was higher in atria and ventricle than in the outflow tract. Thus, HCN channels are specifically distributed and control finely atrial, ventricular and outflow tract pacemakers as well as conduction in the embryonic heart under normoxia and throughout anoxia-reoxygenation.


Assuntos
Antiarrítmicos/farmacologia , Arritmias Cardíacas/prevenção & controle , Benzazepinas/farmacologia , Canais de Cátion Regulados por Nucleotídeos Cíclicos/antagonistas & inibidores , Sistema de Condução Cardíaco/efeitos dos fármacos , Coração/efeitos dos fármacos , Hipóxia/tratamento farmacológico , Oxigênio/metabolismo , Animais , Arritmias Cardíacas/embriologia , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Relógios Biológicos/efeitos dos fármacos , Western Blotting , Embrião de Galinha , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eletrocardiografia , Acoplamento Excitação-Contração/efeitos dos fármacos , Coração/embriologia , Coração/fisiopatologia , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/metabolismo , Sistema de Condução Cardíaco/embriologia , Sistema de Condução Cardíaco/metabolismo , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Hipóxia/embriologia , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Ivabradina , Contração Miocárdica/efeitos dos fármacos , Canais de Potássio/metabolismo , Fatores de Tempo , Técnicas de Cultura de Tecidos
19.
Mol Cell Biochem ; 313(1-2): 133-8, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18418700

RESUMO

Whether the response of the fetal heart to ischemia-reperfusion is associated with activation of the c-Jun N-terminal kinase (JNK) pathway is not known. In contrast, involvement of the sarcolemmal L-type Ca2+ channel (LCC) and the mitochondrial KATP (mitoKATP) channel has been established. This work aimed at investigating the profile of JNK activity during anoxia-reoxygenation and its modulation by LCC and mitoK(ATP) channel. Hearts isolated from 4-day-old chick embryos were submitted to anoxia (30 min) and reoxygenation (60 min). Using the kinase assay method, the profile of JNK activity in the ventricle was determined every 10 min throughout anoxia-reoxygenation. Effects on JNK activity of the LCC blocker verapamil (10 nM), the mitoK(ATP) channel opener diazoxide (50 microM) and the blocker 5-hydroxydecanoate (5-HD, 500 microM), the mitochondrial Ca2+ uniporter (MCU) inhibitor Ru360 (10 microM), and the antioxidant N-(2-mercaptopropionyl) glycine (MPG, 1 mM) were determined. In untreated hearts, JNK activity was increased by 40% during anoxia and peaked fivefold relative to basal level after 30-40 min reoxygenation. This peak value was reduced by half by diazoxide and was tripled by 5-HD. Furthermore, the 5-HD-mediated stimulation of JNK activity during reoxygenation was abolished by diazoxide, verapamil or Ru360. MPG had no effect on JNK activity, whatever the conditions. None of the tested pharmacological agents altered JNK activity under basal normoxic conditions. Thus, in the embryonic heart, JNK activity exhibits a characteristic pattern during anoxia and reoxygenation and the respective open-state of LCC, MCU and mitoKATP channel can be a major determinant of JNK activity in a ROS-independent manner.


Assuntos
Cálcio/metabolismo , Coração/embriologia , Hipóxia/enzimologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Canais de Potássio/metabolismo , Animais , Canais de Cálcio/metabolismo , Galinhas , Estabilidade Enzimática , Ventrículos do Coração/embriologia , Ventrículos do Coração/enzimologia , Técnicas In Vitro , Ativação do Canal Iônico , Modelos Biológicos , Sarcolema/metabolismo
20.
J Hypertens ; 23(4): 785-92, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15775783

RESUMO

OBJECTIVE: This study was performed to test the significance of urinary angiotensinogen (UAGT) in essential hypertensive patients stratified as a function of plasma renin and aldosterone. METHODS AND RESULTS: A sample of 248 essential hypertensives, investigated under their usual sodium diet and either off-medication or under a standardized treatment, was separated into two groups on the basis of upright plasma active renin and aldosterone medians. Patients with plasma active renin and aldosterone below medians are referred to as the low renin-aldosterone essential hypertensive group (LRA-EH). Others subjects are defined as other essential hypertensives (O-EH). Blood pressure (BP) was recorded by 24-h ambulatory monitoring. UAGT was measured by a specific enzyme-linked immunosorbent assay for total angiotensinogen. Because UAGT was markedly increased in the presence of overt proteinuria (>/= 300 mg/24 h), proteinuric patients (n = 29) were excluded from subsequent analyses. UAGT was a significant predictor of systolic and diastolic BP in LRA-EH females (P < 0.01 and P = 0.05, respectively) but not in males. By contrast, urinary sodium excretion (P < 0.001) and maintenance of treatment (P = 0.002) were significant predictors of systolic BP in males. These correlations were not observed in O-EH, whether males or females. CONCLUSIONS: In the present study, UAGT stands as a strong predictor of BP in women with low plasma renin/aldosterone, suggesting an involvement of the tubular renin-angiotensin system in these subjects. Higher sodium intake or the need to maintain treatment may account in part for the lack of a similar relationship in males.


Assuntos
Aldosterona/sangue , Angiotensinogênio/urina , Hipertensão Renal/urina , Sistema Renina-Angiotensina/fisiologia , Renina/sangue , Idoso , Pressão Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteinúria/urina , Fatores Sexuais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA