Abstract 155: Lipopolysaccharide Selectively Decreases Circulating Endothelial Progenitor Cells in Female Mice via Superoxide Production

Abstract

Background: Gender differences exist in cardiovascular disease such as coronary artery disease. Differences also exist between males and females in regard to oxidative stress, which is considered an important mechanism in the development of cardiovascular disease such as atherosclerosis. Endothelial progenitor cells (EPCs) play a critical role in maintaining the structural and functional integrity of vasculature. The number and function of EPCs are closely associated with the outcome for patients with cardiovascular diseases. The objective of the present study was to determine if the effect of oxidative stress on EPCs could differ between males and females. Methods: Male and female wild-type C57BL/6 mice were injected with low dose lipopolysaccharide (LPS) for three days to induce oxidative stress with PBS as control. To evaluate the role of superoxide in mediating the effect of LPS, the mice were treated with superoxide dismutase (SOD) prior to LPS challenge. The blood cells were collected and prepared to determine the populations of EPCs and the levels of intracellular reactive oxygen species (ROS), cytokines, and apoptosis using flow cytometry analysis. Results: The number of circulating EPCs was significantly higher in females than males at baseline. There were no differences in the basal levels of apoptosis and intracellular ROS between males and females. LPS treatment significantly increased levels of the serum inflammatory cytokines including IL-1β and TNF-α in both males and females, suggesting that LPS-induced oxidative stress mouse model was successful. Treatment with LPS significantly decreased the number of circulating EPCs in females, not in males. Treatment with SOD effectively prevented LPS-induced reduction of circulating EPC population in female mice with no effect on EPC population in males. Conclusion: The basal level of circulating EPCs was significantly higher in females than in males independent of intracellular ROS formation and apoptosis. LPS selectively decreased the circulating EPC population in females via superoxide production.