title: Improvement of function and morphology of tumor necrosis factor-alpha treated endothelial cells with 17-beta 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-alpha (TNF-alpha) 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-beta estradiol (E2) can stimulate eNOS production and improve the critical features of atherosclerosis. Using TNF-alpha and E2, we attempted to develop an in vitro vascular model for studying atherosclerosis.
  
  
  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-alpha (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.
  
  
  CONCLUSIONS
  17-beta 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.
authors.affiliation: Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Parin
authors.initials: P
authors.lastname: Suwannaprapha
authors.forename: Urai
authors.initials: U
authors.lastname: Chaisri
authors.forename: Doungrat
authors.initials: D
authors.lastname: Riyong
authors.forename: Yaowapa
authors.initials: Y
authors.lastname: Maneerat
mesh_terms: D001161:Arteriosclerosis / Q000503:physiopathology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology* / Q000648:ultrastructure; D004958:Estradiol / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III