Association Of Hepatocyte Growth Factor And Angiotensin-converting Enzyme With Endothelial Damage In Pregnancy-induced Hypertension

Pregnancy - induced hypertension ( PIH) is a pregnancy - specific disease that causes fetal growth retardation, infant morbidity and mortality, premature birth, and maternal death. This disease is considered to be one of the most significant health problems in human pregnancy, complicating about 6% to 8% of all gestations of more than 20 weeks, especially in the northeast of China. Now, it is widely accepted that endothelial damage may contribute to the central patho-physiological changes observed in PIH, but the cause is not clearly understood.Many factors in systemic and local area are related to the functions of vascular endothelial cells ( VEC). Among them, hepatocyte growth factor ( HGF) , with the c - met proto - oncogene product as its receptor, is specific to VEC, and has the most potent mitogenetic role, besides antiapoptotic effect, endothelial barrier function enhancement, endothelium - dependent relaxtion, and so on. Angiotensin - converting enzyme (ACE) is pivotal to the synthesis of angiotensin II , which has a strong negative regulation of HGF. Recently, we reported that the activity of circulating ACE was elevated, and positively correlated with the severity of PIH, but there are still no reports about the changes of systemic HGF and local HGF and ACE in VEC and the relationship between them.Because of the difficulty of clinical research, endothelial cells cultured in preeclamptic serum, plasma or placental preparation are widely used for the study of endothelial damage in PIH. Now the endothelial cytotoxicity of serum and plasma remains controversial, but the conclusions about the placental preparation are consistent. As the origination of circulating endothelial " toxic" factor in PIH, placental preparation is presumed to be the best choice among them for the study of endothelial damage in PIH, but the theoretical evidence is absent.There are three methods for the preparation of placental conditioned medium, i. e. placental syncytiotrophoblast microvillous membranes (STBM) , pla-cental tissue cultures, and placental hydrosoluble extracts. The research about STEM is the most abundant among them. The reports about placental hydrosolu-ble extracts are not very much, but established results suggested that they could inhibit the proliferation of endothelial cells to the same extent as STBM could. By comparison to STBM, the preparation of placental hydrosoluble extracts is brief and the extracts can be used as medium directly, which can reduce degra-dation of the possible cytotoxic factors. Also, the one - time preparation amount is large, which can provide sufficient specimen for the posterior study, but its feasibility to be applied for the study of endothelial damage in PIH is still under investigation.Accordingly, the objectives of this study lie in; ( 1) To investigate the change of circulating HGF concentration and its relationship with endothelial damage in PIH; (2) To explore a much suitable in vitro coculture system among serum, plasma and placental preparation for the study of endothelial damage in PIH; (3) To prove the feasibility of placental hydrosoluble extracts for the study of endothelial damage in PIH; (4) Based on the in vitro coculture system, to investigate the changes of endothelial HGF system (including HGF and c - met) and ACE in PIH, and the relationship bwteen them.Methods1. The change of circulating HGF concentration and its relationship with endothelial damage in PIH.10 women with PIH (3 mild, 7 moderate and severe PIH) and 10 women with normal pregnancy (NP) were recruited as case group and control group, respectively. For each woman with PIH a healthy pregnancy control was found who was matched for age ( 4 years) , parity (0, 1 to 3, 4) , and gestational age ( 13 days). Enzyme - linked immunoadsordent assay was used to measure the concentration of serum HGF, and flow cytometer was used for counting the number of peripheral blood circulating endothelial cells ( CEC). Results wereanalyzed by two - tailed paired - samples T test and Bivariate corre...