184. High density lipoproteins lose their antioxidant protective effect during pre-eclampsia

Abstract

Introduction Pre-eclampsia (PE) is a hypertensive disorder of pregnancy associated with abnormal placentation leading to poor placental perfusion, oxidative stress, and inflammation, which then leads to the dysfunction of the maternal endothelium. High density lipoproteins (HDL) exert protective effects on the vascular endothelium especially an antioxidant effect. However, HDL can become dysfunctional and lose these protective properties. A dyslipidemia characterized by low plasma levels of HDL, elevated triglycerides, and high levels of low density lipoprotein (LDL)-cholesterol associated with an increased LDL oxidation has been described in PE. Objective/hypothesis We hypothesized that HDL become dysfunctional in PE especially with regard to their antioxidant properties and fail to protect the maternal endothelium. Our study is therefore investigating these antioxidant properties. Methods We conducted a case-control study in 10 pregnant women with early severe PE paired for age and gestational age to 10 control healthy pregnant women. We isolated HDL from patients and control women by ultracentrifugation, and then incubated cultured human endothelial cells with the purified HDL, LDL and CuSO4 for 6 h. Then, we measured TBARs (ThioBarbituric Acid Reactive Substances) produced in culture supernatants to evaluate the HDL antioxidant protective effect. Results The TBARs levels in culture supernatants were significantly raised when the endothelial cells were incubated with HDL purified from PE women rather than with HDL purified from control women (respectively 3.24 ± 1.25 μM versus 2.50 ± 0.95 μM, mean ± SD, p = 0.02). These data show that HDL from PE patients have less antioxidant effect than HDL from pregnant controls. Discussion In our study, we found that HDL isolated from PE patients lose their antioxidant properties, which could explain the increase of oxidized LDL previously described in the PE. These dysfunctional HDL could fail to protect the vascular endothelium; such mechanism could be involved in the physiopathology of the PE endothelium dysfunction.