Tanshinone II-A is protective against human umbilical vein endothelial cell injury after exposure to serum from preeclampsia patients.

BACKGROUND/AIMS: Preeclampsia (PE) is one of the most common and dangerous complications during pregnancy and is characterized by high blood pressure and significant amounts of protein in the urine. Vascular endothelial cell dysfunction is the major pathology in PE. This study was designed to assay the effects of tanshinone II-A (TII-A) on human umbilical vein endothelial cell (HUVEC) injury after incubation with serum from PE patients and to determine the underlying mechanism. METHODS: After treating HUVECs with different TII-A concentrations, cell viability, apoptosis and CD40/CD40 ligand (CD40L) mRNA and protein expression levels were measured. RESULTS: Incubation of HUVECs with serum from PE patients induced morphological alterations, caused decreased cell viability and increased the rate of apoptosis. However, TII-A (5-40 µg/ml) significantly reversed these injuries. Importantly, preapplication of TII-A attenuated PE sera-induced expression of CD40 and CD40L mRNA and protein. CONCLUSION: TII-A has a protective effect against PE sera, likely through regulation of the CD40/CD40L signal transduction pathway.

Preeclampsia serum upregulates CD40/CD40L expression and induces apoptosis in human umbilical cord endothelial cells.

BACKGROUND: The endothelial cell dysfunction observed in preeclampsia (PE) may be induced by CD40/CD40L signaling. This study investigated the role of CD40/CD40L in the pathogenesis of PE by comparing the effect of maternal serum obtained from healthy pregnant women and PE patients on HUVEC cell growth, apoptosis and CD40/CD40L expression. METHODS: Maternal serum was obtained from 20 patients with PE (PE group) as well as 20 healthy pregnant women (control group). The human umbilical endothelial cell line, CRL1730, was cultured in the presence of maternal serum for 24, 48, and 72 h after which cell growth and apoptosis were assessed by MTT and flow cytometry analysis, respectively. CD40/CD40L expression was determined using flow cytometry and RT-PCR analyses. RESULTS: As compared to CRL1730 cells treated with control sera, those treated with PE sera had altered morphology, decreased cell growth, increased apoptosis and greater CD40/CD40L protein and mRNA expression. Stimulation of CD40/CD40L protein and mRNA expression by PE sera was greatest at 24 h. CONCLUSIONS: PE sera may induce endothelial cell damage possibly through increased CD40/CD40L expression in early-onset PE. Further studies are necessary to determine the factor(s) in PE sera responsible for the observed changes in endothelial cell viability.