Vascular endothelial cells express a functional fas-receptor due to lack of hemodynamic forces.
The fas system is present in atherosclerotic lesions. However, its role in the initiation and progression is still unclear. Here we show that in endothelial cells (EC) the expression of the fas receptor is regulated by flow conditions. The EC of the vascular system are regularly exposed to a range of hemodynamic forces with great impact on cellular structures and functions. Recently it was reported that in endothelial cells the lack of hemodynamic forces as well as irregular flow conditions trigger apoptosis by induction of a mechanosensitive autocrine loop of thrombospondin-1 and the alpha(V)beta(3) integrin/integrin-associated protein complex. Here we show that EC cultivated under regular laminar flow conditions are devoid of the fas-receptor whereas cultivation under static conditions as well as under turbulence leads to its expression. Stimulation of the fas-receptor by its ligand increases the amount of apoptotic cells by twofold; the increase can be prevented by blocking the fas-receptor. The availability of the expressed fas receptor for stimulation by its ligand hints at a role as a tool for progression of atherosclerosis.
Freyberg
M A
MA
TU Darmstadt, Institut für Biochemie, Petersenstrasse 22, D-64287 Darmstadt, Germany.
Kaiser
D
D
Graf
R
R
Friedl
P
P
D017209:Apoptosis; D001161:Arteriosclerosis / Q000209:etiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006439:Hemodynamics; D006801:Humans; D013314:Stress, Mechanical; D019014:fas Receptor / Q000378:metabolism* / Q000502:physiology*
D019014:fas Receptor