RESUMO
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.
Assuntos
Adulto , Feminino , Humanos , Masculino , /genética , Expressão Gênica/genética , Estenose da Valva Mitral/genética , Receptor de Endotelina A/genética , Receptor de Endotelina B/genética , Cardiopatia Reumática/genética , /metabolismo , Implante de Prótese de Valva Cardíaca , Estenose da Valva Mitral/cirurgia , Receptor de Endotelina A/metabolismo , Receptor de Endotelina B/metabolismo , Cardiopatia Reumática/metabolismo , Cardiopatia Reumática/cirurgiaRESUMO
El objetivo de la presenta revisión es describir los conceptos actuales sobre el mecanismo local de la cascada de desarrollo y regresión del cuerpo lúteo (CL) regulado por macrófagos, células inmunológicas y citoquinas. El CL de la vaca es un órgano dinámico, el cual tiene una vida media de aproximadamente 17 a 18 días. La principal función del CL es secretar grandes cantidades de progesterona (P4). Cuando el CL madura, las células esteroidogénicas establecen contacto con muchos capilares. Además, el CL maduro está compuesto de muchas células endoteliales vasculares, las cuales pueden alcanzar hasta el 50 % de todas las células del CL. En el ganado bovino y otras especies, el CL juega un papel central en la regulación de la ciclicidad y en el mantenimiento de la preñez. En muchas especies, la regresión luteal es iniciada por la liberación uterina de prostaglandina F2α (PGF2α), la cual inhibe la esteroidogénesis, desencadenando una cascada de eventos que llevan a la desaparición final del tejido. Las células inmunes, principalmente los macrófagos y los linfocitos T, son importantes para la ingestión de los restos celulares que resultan de la muerte de las células luteales. Los macrófagos son células multifuncionales que juegan un papel clave en la respuesta inmune y son abundantes en todo el tejido reproductivo de la hembra. Su localización específica y las variaciones de la distribución en el ovario durante los diferentes estados del ciclo, sugieren que los macrófagos juegan diversas funciones en los eventos intraováricos, lo que incluye: la foliculogénesis, la reestructuración del tejido en la ovulación y la formación y regresión del CL.
The aim of the present review is to describe the current concepts of the local mechanism for the cascade of development and regression of the corpus luteum (CL) as regulated by macrophages, immunological cells and cytokines. The cow CL is a dynamic organ which has a life time of approximately 17-18 days. The main function of the CL is to secrete a large amount of progesterone (P4). As the CL matures, the steroidogenic cells establish contact with many capillaries and the matured CL is composed of many vascular endothelial cells that account for up to 50 % of all CL cells. In cattle and other species, the CL plays a central role in the regulation of cyclicity and maintenance of pregnancy. In many species, luteal regression is initiated by uterine release of PGF2α, which inhibits steroidogenesis and may launch a cascade of events leading to the tissue final disappearance. Immune cells, primarily macrophages and T lymphocites are important for ingestion of cellular remnants that result from the death of luteal cells. Macrophages are multifunctional cells that play key roles in the immune response and are abundant throughout female reproductive tissues. Their specific localization and variations in distribution in the ovary during different stages of the cycle, suggest that macrophages play diverse roles in intra-ovarian events including folliculogenese, tissue restructuring at ovulation and CL formation and regression.
RESUMO
La familia de las endotelinas (ET), está constituida por tres isoformas de 21 aminoácidos: endotelina-1 (ET-1), endotelina-2 (ET-2) y endotelina-3 (ET-3). Las ET son potentes agentes presores endógenos, secretadas por diferentes tejidos y células del organismo. De las tres isoformas, la ET-1 es sintetizada predominantemente por el endotelio vascular. La ET- 1 induce vasoconstricción, es proinflamatoria, profibrosis y tiene acción potencialmente mitógena. Es un importante factor en la regulación del tono vascular y participa en la remodelación vascular. Estos efectos son mediados a través de dos tipos de receptores, ET A y ET B. Los receptores ET A están localizados principalmente en el músculo liso vascular y son responsables de inducir la proliferación celular y vasoconstricción. Los receptores ET B están presentes en las células endoteliales y son mediadores de la relajación vascular por activación de la producción de óxido nítrico y prostaciclina, además, intervienen en la depuración de la ET-1. El sistema endotelina está involucrado esencialmente con la hipertensión arterial sistémica, hipertensión pulmonar, aterosclerosis, reestenosis coronaria, falla cardíaca, cardiomiopatías e insuficiencia renal.
The endothelins (ET S) family consists of three 21 aminoacid isoforms: endothelin-1 (ET-1), endothelin-2 (ET-2) and endothelin-3 (ET-3). ET S are very potent endogenous pressor agents, secreted by various cells and tissues in the human body. Of the three, endothelin-1 is the predominant isoform produced by the vascular endothelium. ET-1 induces vasoconstriction, is proinflammatory, profibrosis, and has mitogenic potential; it is also an important factor in the regulation of vascular tone and arterial vascular remodeling. These effects are mediated via two receptor types, ET A and ET B. ET A receptor is located mainly on vascular smooth muscle and is responsible for mediating vasoconstriction and proliferation. The ET B receptor is present predominantly on endothelial cells and mediates vasorelaxation for NO and prostacyclin release and also ET-1 clearance. The ET system is activated in essential hypertension, pulmonary hypertension, atherosclerosis, coronary restenosis, heart failure, idiopathic cardiomyopathy and renal failure.