The Role Of Leptin In The Pathogenesis Of Preeclampsia

Preeclampsia is a pregnancy specific disorder diagnosed by the new appearance of increased blood pressure and proteinuria in late pregnancy. The symptoms are disappeared after the delivery. It is a leading cause of perinatal morbidity and mortality. The pathogenesis of preeclampsia remains unknown. The endothelial cell dysfunction is considered as a key feature in the pathogenesis of this disease, and placental ischemia is the initiating event in preeclampsia that lead to widespread dysfunction of maternal vascular endothelium.Leptin is a 16 kDa peptide and encoded by ob gene in the adipose tissue. It is involved in the regulation of energy homeostasis as well as the neuroendocrine and reproductive systems. Human placenta is now recognized to be another source of leptin. Many studies reported that Leptin plasma concentrations are increased in preeclampsia. It also have been suggested that leptin contributed to the pathogenesis of obesity-associated hypertension and atherosclerosis. However, the role and mechanism of leptin in preeclampsia has not been reported. We have preformed the following investigation: 1. the effect of hypoxia on production of leptin in human placental tissue, 2 the effect of leptin on function of endothelial cell.1. Measurement of the serum leptin levels in the peripheral vein and uterine vein of preeclamptic women. Serum samples were obtained from pregnancies terminated by cesarean section before labor in Tangdu Hospital ofThe Fourth Military Medical University and Fangzhi Hospital of the Shaanxi province from September 2003 to June 2004. Fifteen preeclamptic women and 20 normotensive pregnant women were recruited in this study. All subjects were healthy before pregnancy. The serum leptin levels were measured by RIA. Mean leptin concentrations were significantly higher in preeclamptic women than in normotensive pregnant women, both in the peripheral vein (P<0.05) and uterine vein (P<0.05). In both groups, the mean leptin concentrations in the peripheral vein were significantly higher than in uterine vein (P<0.05).2. Measurement of the leptin secretion in placental villous explants under hypoxic condition. Placentas were obtained from 8 women undergoing elective cesarian section with normal pregnancies at term in Tangdu Hospital of The Fourth Military Medical University from April 2004 to June 2004. Placental villous explants were cultured under hypoxic conditions. The mean leptin levels were measured by RIA. Mean leptin concentrations were significantly higher in hypoxic conditioned media than normoxic conditioned media (P<0.05).3. Measurement of the mean ET-1 levels and the quantification of VCAM-1. The human umbilical vein endothelial cells (HUVECs) were subjected to human recombinant leptin, then the quantification of VCAM-1 in the cell surface was analyzed by flow cytometry, and the ET-1 contents of cell culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA). Recombinant leptin induced the overexpression of VCAM-1 and ET-1 in endothelial cell (P<0.05).Present results suggest the synthesis of leptin in preeclamptic placenta is increased. Hypoxia in placenta may be an. important factor that results in preeclamptic placenta to produce more leptin. We also found that leptin...