| Objective:Preeclampsia is a pregnancy-specific syndrome of hypertension and proteinuria, resulting in maternal and neonatal morbidity and mortality. Although the fundamental pathogenic mechanisms of the disorder are not well understood, preeclampsia is believed to be associated with utero-placental ischemia and maternal endothelial cell dysfunction. It is a widely held view that "toxic factors" secreted by the placenta into the maternal circulation are responsible for systemic endothelial dysfunction, hypertension, and multi-organ damage. Recent research has shown that soluble Fms-like tyrosine kinase-1 (sFlt-1) is one of the crucial "toxic factors" released by the placenta into the maternal circulation and that it contributes to the hypertension, proteinuria, and endothelial cell dysfunction associated with this disorder. sFlt-1 is a soluble form of the vascular endothelial growth factor receptor that lacks the cytoplasmic tail and transmembrane domain but retains the extracellular ligand-binding domain (sFlt-1 is also named sVEGFRl).Therefore, sFlt-1 prevents circulating vascular endothelial growth factor(VEGF) and placental growth factor (P1GF) interactions with their proangiogenic receptors and functions as an antiangio-genic factor. The level of sFlt-1 in the plasma of women with preeclampsia is elevated in comparison with that in women with uncomplicated pregnancies, a feature consistent with microarray data showing that sFlt-1 mRNA levels are elevated in placentas from women with preeclampsia compared with placentas of normotensive pregnant women. The physiological consequences of elevated sFlt-1 in preeclampsia have been examined recently in animal studies. Administration of sFlt-1 to rats resulted in elevated blood pressure,proteinuria, and renal changes, indicating that excessiveplacental-derived sFlt-1 may contribute to these classic features preeclampsia. In view of the critical contributions of sFltl to disease pathogenesis, it is important to identify factors responsible for increased synthesis and secretion of sFlt-1 by the placentas of women with preeclampsia. Research Methods:BeWo cells were treated with Angiotensin II and its receptor blocker(Valsartan)for 3 days in vitro.The protain levels of sF1t-1 were detected by Enzyme-linked immunosorbent assay (ELISA) in medium supernatant.BeWo Cell culture:All experiments, BeWo cultured cells were divided into 4 groups,(1) control group:95% hamF-12 culture medium+5% FBS(2) study groupl:95% hamF-12 culture medium+5% FBS+100nmol/L angiotensin II(3) study group2:95% hamF-12 culture medium+5% FBS+100nmol/L valsartan(4) study group3:95% hamF-12 culture medium+5% FBS+100 nmol/L angiotensin II+100 nmol/L valsartanResults:In Study Group 1, sF1t-1 average concentration (365.56±30.55pg/ml in culture supernatants) increased significantly compared with the other three groups (sFlt-1 average concentration is 245.76±26.09pg/ml,259.31±15.42 pg/ml, 268.53±23.79 pg/ml in culture supernatant), the difference was statistically significant (p<0.05). There was significant elevation of sFlt-1 expression in BeWo cells treated by AngiotensinⅡ. AngiotensinⅡreceptor blockers can block the effects of angiotensinⅡon the cell in secretion of sFlt-1.Conclusion:Angiotensin stimulates the synthesis and secretion of sFlt-1 via AT1 receptor activation in.cultured choriocarcinoma BeWo cell lines.Significance:This study demonstrate that angiotensin induces sFlt-1 production via angiotensin receptor activation. These findings provide a new way of thinking about the abnormalities associated with preeclampsia.
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