Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Assunto da revista
País de afiliação
Intervalo de ano de publicação
1.
Thromb Res ; 197: 36-43, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33166900

RESUMO

Patients with essential hypertension (EH) and hyperhomocysteinemia (HHCY) suffer from more increased thrombotic events than those in EH alone. However, the underlying mechanisms for this effect are not well understood. This study hypothesized that neutrophil extracellular trap (NET) releasing may be triggered by HHCY in patients in EH, thereby predisposing them to a more hypercoagulable state. Using a modified-capture enzyme-linked immunosorbent assay (ELISA) method, we observed that cell-free DNA (CF-DNA) and myeloperoxidase DNA (MPO-DNA) in patients With EH and HHCY were significantly higher. The NET formation was also positively correlated with homocysteine levels, neutrophil-lymphocyte ratio (NLR), and hypercoagulable markers (thrombin-antithrombin complex, D-dimers). Furthermore, neutrophils from patients in EH with HHCY were found to be predisposed to amplified NET release when compared to patients in EH without HHCY or CTR. Coagulation function assays showed that NETs in patients With EH and HHCY resulted in a significantly increased ability to generate thrombin and fibrin than in those in EH without HHCY or CTR. These procoagulant effects of NETs in patients With EH and HHCY were markedly inhibited (approximately 70%) by the cleavage of NETs with DNase I. Isolated NETs from patients With EH and HHCY neutrophils also exerted a strong cytotoxic effect on endothelial cells (ECs), converted them to apoptosis. This study revealed a previously unrecognized association between the hypercoagulable state and neutrophils in patients With EH and HHCY. Therefore, blocking NETs may represent a new therapeutic objective for preventing thrombosis in these patients.


Assuntos
Armadilhas Extracelulares , Hiper-Homocisteinemia , Coagulação Sanguínea , Células Endoteliais , Hipertensão Essencial , Humanos , Hiper-Homocisteinemia/complicações , Neutrófilos
2.
Acta Pharmacol Sin ; 29(11): 1313-8, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18954525

RESUMO

AIM: To determine whether different Na+/K+-ATPase signal transduction pathways have positive inotropic effects on normal ventricular myocytes (NC) and failing ventricular myocytes (FC), and are involved in an increase of [Ca2+]i induced by strophanthidin (Str). METHODS: A guinea pig model of congestive heart failure was made by constricting descending aorta. The left ventricular myocytes were enzymatically isolated. The effects of 25 micromol/L Str with different signal-transducing inhibitors on contractility and the calcium transient of NC or FC from guinea pigs were simultaneously assessed and compared with those in the 25 micromol/L Str-only group by a video-based, motion-edge detection system. RESULTS: Str at 1, 10, and 25 micromol/L in NC and Str at 0.1, 1, 10, and 25 micromol/L) in FC elevated the calcium transient amplitude and increased the positive inotropic effects in a concentration-dependent manner, respectively. At the same concentration, the effects of Str were more potent in FC than in NC. In FC, both the mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS) signal transduction pathway of Na+/K+-ATPase were involved in the increase of the calcium transient induced by Str, but only activation of the MAPK pathway increased the calcium transient in NC. However, only the ROS pathway was involved in positive inotropic effects both in NC and FC. CONCLUSION: The present study suggests that Na+/K+-ATPase signaling pathways involved in the inotropic effects of Str in NC and FC are consistent, and Na+/K+-ATPase signaling pathways involved in the increase of [Ca2+]i by Str in NC and FC are different.


Assuntos
Cálcio/farmacologia , Miócitos Cardíacos/metabolismo , Transdução de Sinais/fisiologia , ATPase Trocadora de Sódio-Potássio/fisiologia , Estrofantidina/farmacologia , Animais , Cobaias , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/citologia , Ventrículos do Coração/efeitos dos fármacos , Técnicas In Vitro , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA