Expression Of Comt, Ptn, Syndecan-1, And RPTPβ In Pre-eclamptic Placenta

Pre-eclampsia is characterized either by new onset or exacerbation of preexisting hypertention beyond the 20 weeks of gestation and by proteinuria, accompanied by some serious complications. Currently, Preeclampsia is still significant reason that increases maternal peripartal mortality and mortality. But its origin and pathogenesis is not clear . As an important endocrine organ during pregnancy , placenta plays a central role in interconnecting mother and fetus. Its metabolic disorder not only affect its own pathological changes, but also plays an important role in the maternal systemic symptoms and fetal metabolism . At present, it is considered that placental oxidative stress and vascular endothelial dysfunction are the main factors of placentation abnormalities in pathology and subsequent pre-eclampsia. The recent studies have shown that Pleiotrophin and its receptor Syndecan-1(SDC-1), receptor protein tyrosine phosphatase beta(RPTPβ) are expressed in placenta. They have an important impact on invasion of trophoblast cells and vascular endothelial injury. PTN/RPTPβcan regulate the metabolism of catecholamines. And RPTPβparticipate in oxidative stress response. As the main degrading enzyme of catecholamine, Catechol-O-methyltransferase (COMT) affects placental vascular function and catecholamine metabolism. Moreover, it is also a major enzyme of catecholamine metabolism in Fetal circulation.Objective: This study was performed to test mRNA level of COMT, PTN, SDC-1 and RPTPβin normal and pre-eclamptic placenta. To investigate the relationship between their expression and placental pathological changes in preeclampsia.Methods: From April 2009 to August 2009, placental tissue from 15 cases of preeclampsia (experimental group) and 10 cases of normal pregnancy(control group) were was collected immediately after cesarean section. The normal pregnant woman had cesarean section for breech presentation and cephalopelvic disproportion. They were all Han Chinese women ,Singleton pregnancies, and primiparity. The mRNA levels for COMT, PTN, SDC-1 and RPTPβwere determined using quantitative real-time PCR method.Results:(1)The RQ values of COMT in the experimental group and in the control group were 3.889±1.557 and 10.215±2.178,respectively. t=8.487 P<0.05 There is significant difference between the two groups.(2)The RQ values of SDC-1 in the experimental group and in the control group were 1.219±0.698 and 5.451±1.605,respectively. t=9.072 P<0.05 There is significant difference between the two groups.(3)The RQ values of RPTP in the experimental group and in the control group were 6.745±2.170 and 13.649±2.539 , respectively. t=7.285 P<0.05 .There is significant difference between the two groups.(4)The RQ values of PTN in the experimental group and in the control group were 1.115±0.353 and 1.390±0.372,respectively. t=1.863 P>0.05. No significant difference between the two groups.Conclusion:( 1 ) COMT expression was significantly downregulated in pre-eclamptic placenta as compared to normal pregnancy. Its degradation on catecholamines in the placenta was diminished. As a result,placental blood vessel contracts and the catecholamine level, NE particularly, is increased in fetal circulation. Decreasing 2-ME owing to COMT deficiency could influence angiogenesis , vascular endothelial damage and repair.( 2 ) Syndecan–1 expression in pre-eclamptic placenta showed a significant decrease. Reduced basic fibroblast growth factor (bFGF) beause of insufficient Syndecan - 1 can lead to vascular endothelial damage and FGR. Due to decreasing combination between Syndecan - 1 and AT - III, activated AT - III reduced and caused imbalance between coagulation and anticoagulation in placenta. Decreasing Syndecan - 1 can promote vascular permeability and leukocyte extravasation. The interaction between Syndecan– 1 and angiotensin II affects its own expression.(3)The PTN mRNA level in pre-eclamptic placenta was similar to normal pregnant women.But RPTPβexpression in pre-eclamptic placenta was significantly diminished. PTN and RPTPβconstituted a signal transduction pathway which affectd connections of cytoskeletal protein. The cytoskeleton structure of placental vascular endothelial cell could be destroyed. The intercellular connection is weak. Vascular endothelium would be easy to injury. The pathway can also regulate the metabolism of catecholamines. RPTPβdeficiency passivated the sodium channel in placenta. Its ability to regulate osmotic pressure inside and outside cells is diminished.And this might increase the placental edema indirectly. RPTPβinactivation was involved in oxidative stress.In conclusion, PTN, SDC-1and RPTPβexpression in pre-eclamptic placenta adversely impacted the stability of endothelial cells and the connection between endothelial cells. Placental vascular endothelium was susceptible to injury. Weakened promoting blood vessel growth and vascular endothelial repair by PTN / RPTPβ, together with decreasing 2-ME owing to COMT deficiency could cause placental vascular endothelial injury being difficult to repair. PTN can strongly inhibit tyrosine hydroxylase, dopamine-b-hydroxylase and dopamine decarboxylase expression, thus reducing catecholamines synthesis. But this effect did not play in the placenta. Decreasing COMT reduce its degradation on L-dopa. Excess L-DOPA can significantly up regulate RPTPβexpression. But RPTPβexpression was diminished. So the adjustment mechanism of PTN / RPTPβon catecholamine need further study. Through NO, HIF-1α, VEGF and other cytokines, COMT,PTN,SDC-1 and RPTPβhave synergistic effect in vasoconstriction, affecting vasodilatation, and endothelial cell injury and repair. They interact to each other and their relationship is actually complicated. Their activity is directly bound up with the pathological changes of placenta in preeclampsia.