Improvement of function and morphology of tumor necrosis factor-α treated endothelial cells with 17-β estradiol - A preliminary study for a feasible simple model for atherosclerosis

Abstract

Background: Dysfunction of endothelial cells (EC) to produce endothelial nitric oxide synthase (eNOS) by tumor necrosis factor-α (TNF-α) causes critical features of vascular inflammation associated with several disease states (eg, atherosclerosis including increased platelet aggregation and adhesion on EC, elevated adhesion molecules and enhanced inflammatory cells binding to EC). 17-β estradiol (E2) can stimulate eNOS production and improve the critical features of atherosclerosis. Using TNF-α and E2, we attempted to develop an in vitro vascular model for studying atherosclerosis. Methods and Results: Human umbilical vein endothelial cells (HUVEC) grown in transwells were cocultured with smooth muscle cells in a 24-well plate to mimic the major components of the vascular wall. The model was incubated with TNF-α (10 ng/ml) for 12 h, prior exposed to E2 (100 pg/ml) for 6-12 h, then investigated by transmission and scanning electron microscopes. The result indicated recovered morphology with good tight junction, and decreased platelet adhesion was noted in defective HUVEC after E2 treatment. Conclusion: 17-β estradiol was represented as an antiatherosclerogenic agent to demonstrate feasibility of the model. Although our finding focused only on the endothelium, this would be the basis for our future studies to develop ex vivo continuous perfusion of human vessel segments for a further atherosclerosis study.