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Oxidized LOw‐density lipoprotein sensitizes human vascular smooth muscle cells to FAS (CD95)‐mediated apoptosis
Author(s) -
Takarada Shigeho,
Imanishi Toshio,
Hano Takuzo,
Nishio Ichiro
Publication year - 2003
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2003.03829.x
Subject(s) - apoptosis , fas receptor , vascular smooth muscle , programmed cell death , dna fragmentation , fas ligand , microbiology and biotechnology , receptor , chemistry , signal transduction , downregulation and upregulation , biology , endocrinology , biochemistry , smooth muscle , gene
Summary 1. It was investigated in the present study whether oxidized low‐density lipoprotein (oxLDL) was implicated in the susceptibility of human vascular smooth muscle cells (VSMC) to Fas‐mediated death. Human fetal aorta smooth muscle cells were treated with agonistic anti‐Fas antibody (CH11) and oxLDL and cell death was then determined by viability and DNA fragmentation. 2. The results of the present study show that cross‐linking of Fas receptor with anti‐Fas antibody in the presence of oxLDL induced death and DNA fragmentation in human VSMC, which were blocked by the caspase inhibitor z‐VAD.fmk, followed by the upregulation of cell surface Fas. 3. The data indicate that oxLDL is implicated in death in VSMC and provide evidence that oxLDL is involved in Fas signal transduction. The present study proposes a novel mechanism(s) by which VSMC become susceptible to Fas ligand. 4. One of the mechanisms proposed by which oxLDL upregulates cell surface Fas is by inhibiting the degradation of Fas through the ubiquitin–proteasome pathway.