title: Senescent endothelial cells are prone to TNF-α-induced cell death due to expression of FAS receptor.
abstract: The senescent endothelial cells show various phenotypes which can increase the incidence of inflammatory cardiovascular diseases, but the fundamental basis for such phenotypic changes of senescing cells remains to be elucidated. This study was undertaken to find transmembrane receptors that might be highly expressed in senescent endothelial cells and play a key role in cell death signal transduction. Comparison of mRNA expression in young and senescent human umbilical vein endothelial cells, using a cDNA microarray method, provided a list of transmembrane receptors including the FAS receptor (tumor necrosis factor receptor superfamily member 6) whose expression levels were significantly increased by cellular senescence. Additional studies focused on FAS demonstrated that a high expression of FAS receptor in senescent endothelial cells is responsible for the susceptibility to apoptotic cell death, as the siRNA-mediated suppression of FAS expression in senescent cells prevented the cell death, and overexpression of exogenous FAS in young cells increased cell death. We also verified that FAS expression level was closely associated with the activation of caspase-3 and caspase-9 involved in apoptosis. The senescence-induced transmembrane receptors including the FAS receptor may provide novel therapeutic targets to prevent cardiovascular diseases.
authors.affiliation: Department of Molecular Medicine, Cell and Matrix Research Institute, BK21 Medical Education Program for Human Resources, Kyungpook National University School of Medicine, Daegu 700-422, South Korea.
authors.forename: Hyeona
authors.initials: H
authors.lastname: Jeon
authors.forename: Yong Chool
authors.initials: YC
authors.lastname: Boo
mesh_terms: D017209:Apoptosis; D002318:Cardiovascular Diseases / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival; D016922:Cellular Senescence; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010957:Plasmids; D034741:RNA, Small Interfering / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: C491901:FAS protein, human; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9
keywords: Cell death; EGFP; Endothelial cells; FAS; FAS receptor; GAPDH; HUVECs; LSS; NO; NOS3; RT-PCR; Senescence; TNF; enhanced green fluorescent protein; glyceraldehyde 3-phosphate dehydrogenase; human umbilical vein endothelial cells; laminar shear stress; nitric oxide; nitric oxide synthase 3; reverse transcriptase-polymerase chain reaction; siRNA; small interfering RNA; tumor necrosis factor; tumor necrosis factor receptor superfamily member 6