Effect of dehydroepiandrosterone on endothelial cell proliferation

The steroid dehydroepiandrosterone (DHEA) is know to have anti-atherosclerotic properties. However, the mechanism by which DHEA exerts its effect is not clear. We hypothesized that DHEA protects against the atherogenic effects of LDL. Therefore attempts were made to test this hypothesis on endothelial cells (EC) in culture. Experiments were performed to determine the effect of DHEA and LDL on EC proliferation. Incubation of DHEA with EC for 24 hours had minimal effect on cell proliferation. However, at 48 hours of incubation, 25 and 50 nanograms DHEA inhibited EC proliferation by 50%. LDL (20 ug) inhibited EC proliferation by 27% and 63% at 24 and 48 hours respectively compared to the corresponding controls. EC proliferation was stimulated by 40% in the presence of 5 ng of DHEA and LDL in 24 hour incubations. However, at 48 hour incubations DHEA negated the inhibitory effect of LDL on EC proliferation. Determination of malondialdehyde (MDA), a measure of oxidative damage shows that in incubations of EC containing 5, 25, and 50 ng of DHEA for 24 hour did not affect the MDA levels. However, at 48 hour incubations, MDA levels were 44% and 50% higher respectively compared to the control. MDA levels increased in EC cultures containing LDL by 259% and 208% at 24 and 48 hours respectively compared to the corresponding controls. EC cultures containing LDL and 5 ng DHEA reduced MDA levels by 62% and 50% at 24 and 48 hours respectively compared to the corresponding controls. These results show that DHEA protects EC against LDL induced cytotoxic effect and suggests a mechanism for anti-atherosclerotic effect of DHEA.