RESUMO
Changes in vascular endothelial growth factor (VEGF) in pulmonary vessels have been described in congenital diaphragmatic hernia (CDH) and may contribute to the development of pulmonary hypoplasia and hypertension; however, how the expression of VEGF receptors changes during fetal lung development in CDH is not understood. The aim of this study was to compare morphological evolution with expression of VEGF receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1), in pseudoglandular, canalicular, and saccular stages of lung development in normal rat fetuses and in fetuses with CDH. Pregnant rats were divided into four groups (n=20 fetuses each) of four different gestational days (GD) 18.5, 19.5, 20.5, 21.5: external control (EC), exposed to olive oil (OO), exposed to 100 mg nitrofen, by gavage, without CDH (N-), and exposed to nitrofen with CDH (CDH) on GD 9.5 (term=22 days). The morphological variables studied were: body weight (BW), total lung weight (TLW), left lung weight, TLW/BW ratio, total lung volume, and left lung volume. The histometric variables studied were: left lung parenchymal area density and left lung parenchymal volume. VEGFR1 and VEGFR2 expression were determined by Western blotting. The data were analyzed using analysis of variance with the Tukey-Kramer post hoc test. CDH frequency was 37% (80/216). All the morphological and histometric variables were reduced in the N- and CDH groups compared with the controls, and reductions were more pronounced in the CDH group (P<0.05) and more evident on GD 20.5 and GD 21.5. Similar results were observed for VEGFR1 and VEGFR2 expression. We conclude that N- and CDH fetuses showed primary pulmonary hypoplasia, with a decrease in VEGFR1 and VEGFR2 expression.
Assuntos
Hérnias Diafragmáticas Congênitas/metabolismo , Pulmão/efeitos dos fármacos , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Hérnias Diafragmáticas Congênitas/induzido quimicamente , Hérnias Diafragmáticas Congênitas/embriologia , Pulmão/embriologia , Éteres Fenílicos , Gravidez , Ratos Sprague-DawleyRESUMO
Changes in vascular endothelial growth factor (VEGF) in pulmonary vessels have been described in congenital diaphragmatic hernia (CDH) and may contribute to the development of pulmonary hypoplasia and hypertension; however, how the expression of VEGF receptors changes during fetal lung development in CDH is not understood. The aim of this study was to compare morphological evolution with expression of VEGF receptors, VEGFR1 (Flt-1) and VEGFR2 (Flk-1), in pseudoglandular, canalicular, and saccular stages of lung development in normal rat fetuses and in fetuses with CDH. Pregnant rats were divided into four groups (n=20 fetuses each) of four different gestational days (GD) 18.5, 19.5, 20.5, 21.5: external control (EC), exposed to olive oil (OO), exposed to 100 mg nitrofen, by gavage, without CDH (N-), and exposed to nitrofen with CDH (CDH) on GD 9.5 (term=22 days). The morphological variables studied were: body weight (BW), total lung weight (TLW), left lung weight, TLW/BW ratio, total lung volume, and left lung volume. The histometric variables studied were: left lung parenchymal area density and left lung parenchymal volume. VEGFR1 and VEGFR2 expression were determined by Western blotting. The data were analyzed using analysis of variance with the Tukey-Kramer post hoc test. CDH frequency was 37% (80/216). All the morphological and histometric variables were reduced in the N- and CDH groups compared with the controls, and reductions were more pronounced in the CDH group (P<0.05) and more evident on GD 20.5 and GD 21.5. Similar results were observed for VEGFR1 and VEGFR2 expression. We conclude that N- and CDH fetuses showed primary pulmonary hypoplasia, with a decrease in VEGFR1 and VEGFR2 expression.
Assuntos
Animais , Feminino , Gravidez , Hérnias Diafragmáticas Congênitas/metabolismo , Pulmão/efeitos dos fármacos , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Modelos Animais de Doenças , Hérnias Diafragmáticas Congênitas/induzido quimicamente , Hérnias Diafragmáticas Congênitas/embriologia , Pulmão/embriologia , Éteres Fenílicos , Ratos Sprague-DawleyAssuntos
Transtorno Bipolar/genética , Proteínas de Transporte/genética , Depressão/genética , Transtorno Distímico/genética , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Polimorfismo Genético , Adulto , Brasil , Estudos de Casos e Controles , Genótipo , Humanos , Pessoa de Meia-Idade , Proteínas da Membrana Plasmática de Transporte de SerotoninaAssuntos
Doença de Alzheimer/genética , Apolipoproteínas E/genética , Proteínas de Transporte/genética , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Polimorfismo Genético , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/epidemiologia , Apolipoproteína E4 , Variação Genética , Humanos , Valores de Referência , Risco , Fatores de Risco , Proteínas da Membrana Plasmática de Transporte de SerotoninaRESUMO
We analyzed a deletion/insertion polymorphism within the promoter region of the serotonin transporter gene (5-HTTPLR) in 81 patients with late onset Alzheimer's (AD) disease (mean age 70.02 +/- 8.13 years). Control groups included 81 normal subjects with comparable age (mean age 75.6 +/- 10.2) and 82 younger normal subjects (mean age 37.4 +/- 9.1). Statistical analysis showed a significant difference in the genotype and gene frequencies between the AD group and normal controls (chi 2 = 9.021; 2 d.f. and chi 2 = 5.59, 1 d.f., respectively, P < 0.05) due to the higher frequency of the L allele and the lower frequency of the s allele in controls than among AD patients. However, no differences were found in the genotype frequencies in older as compared to younger normal control groups (chi 2 = 0.337, 2 d.f. and P > 0.05). The present study confirms, in a different population, that the short variant of the 5-HTTPLR polymorphism may be a risk factor for late onset AD.
