Oxidized low density lipoprotein potentiation of Fas-induced apoptosis through lectin-like oxidized-low density lipoprotein receptor-1 in human umbilical vascular endothelial cells.
Under normal conditions, vascular endothelial cells are resistant to Fas-mediated apoptosis, although they express detectable Fas on their cell surface. Because oxidized Low density lipoprotein (Ox-LDL) is thought to promote atherogenesis, the potential role that Ox-LDL may play in Fas-mediated apoptosis was investigated in human umbilical vascular endothelial cells (HUVECs), focusing particularly on the involvement of the lectin-like Ox-LDL receptor-1 (LOX-1). HUVECs were treated with agonistic anti-Fas antibody (CH11) and Ox-LDL and then the degree of apoptosis was determined by cell death ELISA. Ox-LDL concentration-dependently sensitized Fas-mediated apoptosis. Flow cytometry demonstrated that Ox-LDL dose-dependently up-regulated cell surface Fas expression. On the other hand, treating HUVECs with Ox-LDL did not lead to any significant change in the expression of death mediators, including Fas, Fas ligand (FasL), FADD, and FLICE as assessed by multiplex polymerase chain reaction amplification. More importantly, these effects of Ox-LDL on Fas-mediated apoptosis were significantly blocked by a neutralizing LOX-1 monoclonal antibody, which can block LOX-1-mediated cellular uptake of Ox-LDL. Ox-LDL may be an important factor involved in the regulation of Fas-induced apoptosis via Ox-LDL/LOX-1 interaction in vascular endothelial cells. The results may provide insights into the pathogenesis of accelerated atherosclerosis in patients with hyperlipidemia.
Imanishi
Toshio
T
Division of Cardiology, Department of Medicine, Wakayama Medical University, Japan. t-imani@wakayama-med.ac.jp
Hano
Takuzo
T
Sawamura
Tatsuya
T
Takarada
Shigeho
S
Nishio
Ichiro
I
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis; D001161:Arteriosclerosis / Q000209:etiology; D002352:Carrier Proteins / Q000235:genetics; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology*; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D008077:Lipoproteins, LDL / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011973:Receptors, LDL / Q000502:physiology*; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D014470:Umbilical Cord / Q000098:blood supply; D015854:Up-Regulation; D019014:fas Receptor / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505533:FADD protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D008077:Lipoproteins, LDL; D008562:Membrane Glycoproteins; C495137:OLR1 protein, human; D012333:RNA, Messenger; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D019014:fas Receptor; C099252:oxidized low density lipoprotein; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases