RESUMEN
OBJECTIVES: Rheumatic fever is a highly prevalent disease in Brazil, and it poses a major public health problem. It is the leading cause of acquired heart disease in childhood and adolescence. The aim of this study was to evaluate the gene expression of ET-3 and its receptors, in replaced rheumatic mitral valves. METHODS: We studied the gene expression of endothelin-3 (ET-3) and its receptors, endothelin receptor A and endothelin receptor B (ETr-A and ETr-B), in the rheumatic mitral valves of 17 patients who underwent valve replacement surgery. The samples also underwent a histological analysis. RESULTS: Our data showed that almost all patients, regardless of individual characteristics such as gender or age, expressed the endothelin receptor genes, but did not express the genes for ET-3. In quantitative analysis, the ETr-A/GAPDH mean ratio was 33.04 ± 18.09%; while the ETr-B/GAPDH mean ratio was 114.58 ± 42.30%. Regarding histopathological individual features, the frequency of fibrosis is 100%, 88.23% of mononuclear infiltrate, 52.94% of neovascularization, 58.82% of calcification and absence of ossification. CONCLUSION: The presence of receptors ETr-A and ETr-B in rheumatic mitral valves suggests its interaction with the system of circulating endothelins, particularly ETr-B (known for acting in the removal of excess endothelin) detected in a greater proportion, which could explain the lack of expression of endothelin in rheumatic mitral valve, process to be elucidated.
OBJETIVOS: A febre reumática é uma doença altamente prevalente no Brasil, e representa um importante problema de saúde pública. É a principal causa de cardiopatia adquirida na infância e adolescência. O objetivo deste estudo foi avaliar a expressão gênica de ET-3 e seus receptores, em valvas mitrais reumáticas substituídas. Métodos: Estudamos a expressão gênica de endotelina-3 (ET-3) e de seus receptores, receptor da endotelina A e receptor da endotelina B (ETr-A e ETr-B), nas valvas mitrais reumáticas de 17 pacientes que se submeteram à cirurgia de troca valvar. As amostras também foram submetidas à análise histológica. RESULTADOS: Nossos dados mostraram que praticamente todos os pacientes, independentemente de características individuais, como sexo ou idade, expressaram os genes de receptores de endotelina, porém não expressaram os genes para ET-3. Na análise quantitativa, a média da proporção ETr-A/GAPDH foi de 33,04 ± 18,09%; enquanto que a média da proporção ETr-B/GAPDH foi de 114,58 ± 42,30%. Em relação às características histopatológicas individuais, a frequência de fibrose foi de 100%, infiltrado mononuclear de 88,23%, neovascularização de 52,94%, calcificação de 58,82% e houve ausência de ossificação. CONCLUSÃO: A presença de receptores ETr-A e ETr-B em valvas mitrais reumáticas sugere sua interação com o sistema de endotelinas circulantes, particularmente ETr-B (reconhecido por atuar na remoção do excesso de endotelina), detectado em maior proporção, o que poderia explicar a ausência da expressão de endotelina em valva mitral reumática, processo a ser elucidado.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , /genética , Expresión Génica/genética , Estenosis de la Válvula Mitral/genética , Receptor de Endotelina A/genética , Receptor de Endotelina B/genética , Cardiopatía Reumática/genética , /metabolismo , Implantación de Prótesis de Válvulas Cardíacas , Estenosis de la Válvula Mitral/cirugía , Receptor de Endotelina A/metabolismo , Receptor de Endotelina B/metabolismo , Cardiopatía Reumática/metabolismo , Cardiopatía Reumática/cirugíaRESUMEN
The purpose of this study was to investigate the therapeutic effects of small hairpin RNA (shRNA) targeting endothelin-converting enzyme (ECE)-1 in monocrotaline (MCT)-induced pulmonary hypertensive rats. Ninty-four Sprague-Dawley rats were divided into three groups: control (n = 24), MCT (n = 35) and shRNA (n = 35). Four-week survival rate in the shRNA group was significantly increased compared to that in the MCT group. The shRNA group showed a significant improvement of right ventricular (RV) pressure compared with the MCT group. The MCT and shRNA groups also showed an increase in RV/(left ventricle + septum) ratio and lung/body weight. Plasma endothelin (ET)-1 concentrations in the shRNA group were lower than those in the MCT group. Medial wall thickness of pulmonary arterioles were increased after MCT injection and was significantly decreased in the shRNA group. The number of intra-acinar muscular pulmonary arteries was decreased in the shRNA group. The mRNA expressions of ET-1 and ET receptor A (ETA) were significantly decreased in the shRNA group in week 4. The protein levels of ETA were decreased in the shRNA group in week 2. The protein levels of tumor necrosis factor-alpha and vascular endothelial growth factor were decreased in the shRNA group in week 4. In conclusion, the gene silencing with lentiviral vector targeting ECE-1 could be effective against hemodynamic, histopathological and gene expression changes in pulmonary hypertension.