RESUMEN
Preeclampsia (PE) is initiated by abnormal placentation in the early stages of pregnancy, followed by systemic activation of endothelial cells of the maternal small arterioles in the late second or third trimester (TM) of pregnancy. During normal pregnancy, placental cytotrophoblasts (CTBs) invade the maternal uterine wall and spiral arteries, whereas this process is interrupted in PE. However, it is not known how the malformed placenta triggers maternal endothelial crisis and the associated manifestations. Here, we have focused on the association of CD81 with PE. CD81, a member of the tetraspanin superfamily, plays significant roles in cell growth, adhesion, and motility. The function of CD81 in human placentation and its association with pregnancy complications are currently unknown. In the present study, we have demonstrated that CD81 was preferentially expressed in normal first TM placentas and progressively down-regulated with gestation advance. In patients with early-onset severe PE (sPE), CD81 expression was significantly up-regulated in syncytiotrophoblasts (STBs), CTBs and the cells in the villous core. In addition, high levels of CD81 were observed in the maternal sera of patients with sPE. Overexpressing CD81 in CTBs significantly decreased CTB invasion, and culturing primary human umbilical vein endothelial cells (HUVECs) in the presence of a high dose of exogenous CD81 resulted in interrupted angiogenesis and endothelial cell activation in vitro. Importantly, the phenotype of human PE was mimicked in the CD81-induced rat model.
Asunto(s)
Placentación/fisiología , Preeclampsia/patología , Tetraspanina 28/metabolismo , Trofoblastos/fisiología , Animales , Biomarcadores/sangre , Adhesión Celular , Movimiento Celular/fisiología , Vellosidades Coriónicas/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Femenino , Células Endoteliales de la Vena Umbilical Humana , Humanos , Inmunohistoquímica , Neovascularización Fisiológica/fisiología , Preeclampsia/sangre , Embarazo , Primer Trimestre del Embarazo , Tercer Trimestre del Embarazo , Cultivo Primario de Células , Ratas , Ratas Sprague-Dawley , Tetraspanina 28/sangre , Regulación hacia Arriba , Útero/irrigación sanguíneaRESUMEN
Nitric oxide generated by endothelial nitric oxide synthase (eNOS) plays an important role in maintaining cardiovascular homeostasis. Under various pathological conditions, abnormal expression of eNOS contributes to endothelial dysfunction and the development of cardiovascular diseases. A variety of pathological stimuli has been reported to decrease eNOS expression mainly through decreasing eNOS mRNA stability by regulating the binding of several cytosolic proteins to the cis-acting sequences within eNOS mRNA 3' untranslated regions. However, the detailed mechanisms remain elusive. Because microRNAs inhibit gene expression through binding to the 3' untranslated regions of their target mRNAs, microRNAs may be the important posttranscriptional modulators of eNOS expression. Here, we provided evidence that eNOS is a direct target of miR-155. Overexpression of miR-155 decreased, whereas inhibition of miR-155 increased, eNOS expression and NO production in human umbilical vein endothelial cells and acetylcholine-induced endothelium-dependent vasorelaxation in human internal mammary arteries. Inflammatory cytokines including tumor necrosis factor-α increased miR-155 expression. Inhibition of miR-155 reversed tumor necrosis factor-α-induced downregulation of eNOS expression and impairment of endothelium-dependent vasorelaxation. Moreover, we observed that simvastatin attenuated tumor necrosis factor-α-induced upregulation of miR-155 and ameliorated the effects of tumor necrosis factor-α on eNOS expression and endothelium-dependent vasodilation. Simvastatin decreased miR-155 expression through interfering mevalonate-geranylgeranyl-pyrophosphate-RhoA signaling pathway. These findings indicated that miR-155 is an essential regulator of eNOS expression and endothelium-dependent vasorelaxation. Inhibition of miR-155 may be a new therapeutic approach to improve endothelial dysfunction during the development of cardiovascular diseases.
Asunto(s)
Endotelio Vascular/metabolismo , Arterias Mamarias/metabolismo , MicroARNs/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Vasodilatación/genética , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/genética , Endotelio Vascular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Arterias Mamarias/efectos de los fármacos , MicroARNs/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Simvastatina/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Vasodilatación/efectos de los fármacosRESUMEN
OBJECTIVE: To estimate the prevalence of hepatitis B surface antigen (HBsAg) among pregnant women in Jiangsu Province, eastern China, 17years after vaccination against hepatitis B virus (HBV) was introduced. METHODS: From August 2002 to July 2004, serum samples from 6398 women between 15 and 20weeks of pregnancy and from 6 urban and 8 rural areas across Jiangsu Province were tested for markers of HBV. The results were then compared with the rates before 1980. RESULTS: The overall rates of 6.71% for HBsAg and 36.84% for anti-HBs were significantly lower and higher, respectively, than the prevaccination rates. The rate for HBsAg was lower in urban areas than in rural areas (5.75% vs 7.14%, P=0.04). Although the rate used to be much higher in the northern part of Jiangsu Province, which is less prosperous than the southern part, the rates are now similar in both parts (6.60% vs 6.97%). CONCLUSION: These findings demonstrate a drop in the prevalence of HBsAg among pregnant women in Jiangsu Province since the introduction of vaccination programs in 1980, and indicate that HBV infection can also be controlled in less prosperous areas.