Amplificação dos genes que codificam a endotelina-1 e seus receptores em valvas mitrais reumáticas / Amplification of the genes that codify endothelin-1 and its receptors in rheumatic mitral valves

FUNDAMENTO: As cardiopatias são doenças de alta prevalência, sendo a cardite reumática uma doença de grande relevância em países em desenvolvimento. As alterações em câmaras cardíacas esquerdas se associam à disfunção endotelial, com aumento dos níveis de endotelina-1 (ET-1) e consequências sobre a circulação pulmonar, muitas vezes determinando a hipertensão pulmonar (HP). No entanto, a presença de ET-1 e seus receptores na própria valva mitral, promovendo alterações vasculares pulmonares e aumentando a deformação valvar reumática, ainda é um assunto não abordado na literatura. OBJETIVO: Determinar, mediante técnicas moleculares, a expressão dos genes da endotelina e dos seus receptores em valvas mitrais reumáticas. MÉTODOS: 27 pacientes submetidos à troca valvar mitral tiveram seu tecido valvar analisado, a fim de determinar a presença de genes de ET-1 e seus receptores A e B. Foram feitas análises histológica e molecular das valvas (divididas em fragmentos M1, M2 e M3) e colhidos dados clínicos e epidemiológicos dos pacientes. Foram divididos em três grupos: valvopatia mitral, mitroaórtica e pacientes reoperados. RESULTADOS: O estudo mostrou a manifestação do gene da ET-1 em 40,7 por cento dos espécimes e de seu receptor A em todas as amostras, com manifestação minoritária do gene do receptor B (22,2 por cento). CONCLUSÃO: Todos os pacientes expressaram a presença do gene do receptor A. Não houve diferença estatística quanto à gravidade da doença, expressa em classe funcional, e aos subgrupos estudados (valvopatas mitrais, mitroaórticos e pacientes reoperados), ou quanto à expressão dos genes da ET-1 e seus receptores entre os subgrupos estudados (valvopatas mitrais, mitroaórticos e pacientes reoperados).

BACKGROUND: Cardiopathies are high prevalence conditions. Among them, rheumatic carditis is of high relevance in developing countries. Left cardiac chamber changes are associated to endothelial dysfunction and ET-1 levels increase. Pulmonary circulation is then affected, and not seldom leading to pulmonary hypertension (PH). However, the presence of ET-1 and its receptors in the mitral valve itself - promoting pulmonary vascular changes, with increased rheumatic valvular deformation - has not been discussed in the literature. OBJECTIVE: To determine the expression of endothelin gene and its receptors in rheumatic mitral valves through techniques of molecular genetics. METHODS: Twenty-seven patients submitted to mitral valve replacement had their valvular tissue examined to determine the presence of ET-1 genes and their A and B receptors. Histological and molecular analysis of the valves was performed (divided into M1, M2 and M3 fragments), with patients' clinical and epidemiological data collected. Patients were divided into 3 groups (mitral valvopathy, mitroaortic valvopathy, and reoperation patients). RESULTS: The study showed endothelin-1 gene expression in 40.7 percent specimens and A receptor in all samples; receptor gene B had lower expression (22.2 percent). CONCLUSION: All patients showed A receptor gene expression. No statistically significant difference was observed in regard to condition severity, expressed according to functional class, and subgroups (mitral valvopathy, mitroaortic valvopathy, and reoperation patients).

Increased expression of endothelin receptors in human cirrhosis--relationship with splanchnic hemodynamics / 华中科技大学学报（医学）（英德文版）

The purpose of the present study was to assess the correlation that likely exists among increased portal pressure (Pp), portal blood flow quantity (Qp) and ETA and ETB receptor mRNA expression in human cirrhosis. In situ hybridization and reverse-transcription polymerase chain reactions (RT-PCR) were performed to determined the expression of ETA and ETB receptor mRNA in liver tissues from traumatic subjects (n = 10) and cirrhotic patients (n = 15) in whom hepatic hemodynamic values were measured. The expression of the two transcripts was significantly higher in liver samples of cirrhotic patients than in those obtained from traumatic subjects. It has shown that ETA receptor mRNA predominantly located in hepatic stellate cells (HSCs) and vascular smooth muscle cells of intrahepatic arteries and portal veins, ETB receptor mRNA in HSCs, sinusoidal endothelial cells and Kuppfer cells. There was a highly significant direct relationship between ETA and ETB receptor mRNA and Pp and Qp in cirrhotic patients. It suggests that liver paracrine endothelin system may be overactivated in human cirrhosis accompanied with increased expression of ETA and ETB receptor mRNA which may play an important role in the pathogenesis and maintenance of splanchnic hyperdynamics.