tanshinone-ii-a-sodium-sulfonate and Pre-Eclampsia

Preeclampsia (PE) is a serious blood pressure disorder of pregnancy. Systemic endothelial cell dysfunction, a hallmark of PE, is previously estimated to be induced by hypoxic trophoblast high mobility group box 1 (HMGB1). In the present study, we investigated the protective effect of sodium tanshinone IIA sulfonate (STS), the soluble form of tanshinone IIA isolated from danshen, against hypoxic trophoblast HMGB1-induced human umbilical vein endothelial cell (HUVEC) dysfunction. Our results showed that HMGB1 expression and release were significantly decreased in STS-treated hypoxic JEG-3 cells. A further study revealed hypoxic trophoblast HMGB1-induced cytotoxicity and leukostasis of HUVEC as well as higher expression of cell adhesion molecules (VCAM-1 and ICAM-1) could be reversed by pretreatment with STS. In conclusion, our study suggests that STS is an effective agent against hypoxic trophoblast-induced cell injury of HUVEC via targeting HMGB1 release and forms the basis of the development of such a compound in treating PE.

Topics: Cell Hypoxia; Endothelial Cells; Female; Gene Expression Regulation; HMGB1 Protein; Human Umbilical Vein Endothelial Cells; Humans; Phenanthrenes; Pre-Eclampsia; Pregnancy; Trophoblasts

Preeclampsia is a disorder of pregnancy with a significant impact on maternal and fetal health. The complexity of this multifactorial condition has precluded development of effective therapies and, although many potential pathways have been investigated, the etiology still requires clarification. Our group has investigated the scavenger lectin-like oxidized LDL (LOX-1) receptor, which may respond to factors released from the distressed placenta that contribute to the vascular pathologies observed in preeclampsia. Given the known beneficial effects of sodium tanshinone IIA sulfonate (STS; a component of Salvia miltiorrhiza) on vasodilation, reduction of oxidative stress, and lipid profiles, we have investigated its role as a potential treatment strategy. We hypothesized that STS would improve vascular endothelial function and, combined with a reduction in oxidative stress, would improve pregnancy outcomes in a rat model of preeclampsia (reduced uteroplacental perfusion pressure, RUPP). We further hypothesized this may occur via the action of STS on the LOX-1 and/or platelet-activating factor (PAF) receptor axes. The RUPP model increased maternal blood pressure, vascular oxidative stress, and involvement of the vascular PAF receptor. Treatment with STS during pregnancy decreased both oxidative stress and involvement of the PAF receptor; however, it also increased involvement of the LOX-1 receptor, which is in line with the concept that scavenger receptors, such as LOX-1 and PAF, are upregulated in response to ligand binding and/or under pathological conditions. In this model of preeclampsia, however, the vascular actions of STS did not lead to improvements in pregnancy outcome such as fetal biometrics or maternal blood pressure.

Topics: Animals; Blood Pressure; Disease Models, Animal; Endothelium, Vascular; Female; Lipoproteins, LDL; Oxidative Stress; Phenanthrenes; Placenta; Pre-Eclampsia; Pregnancy; Rats, Sprague-Dawley; Vasodilation