title: Shear stress induces apoptosis in vascular smooth muscle cells via an autocrine Fas/FasL pathway.
abstract: Endothelial lesions may lead to the exposure of vascular smooth muscle cells (VSMCs) to the blood flow. In such circumstances VSMCs are exposed to shear stress, an extraordinary mechanical stimulus for this type of cells. Rat VSMCs are cultivated in normal tissue culture plates (statically) or in a cone-plate viscometer (dynamically). Dynamic cultivation leads to a great increase of apoptosis. Immunofluorescence reveals the shear-stress-dependent expression of fas. Apoptosis can be induced by addition of fas ligand-a process which can be blocked by antibodies against either fas or fas ligand. Conditioned medium of dynamically cultivated VSMCs contains fas ligand as the only active apoptosis inducing activity. Apoptosis can be blocked by caspase inhibitors. So the exposure of VSMCs to shear stress leads to apoptosis by the establishment of an autocrine loop of fas and fas ligand-a potential mechanism for the prevention of narrowing of vessel diameter by VSMC proliferation.
authors.affiliation: Technische Universität Darmstadt, CSI für. Org.Chemie and Biochemie, Petersenstr. 22, Darmstadt D-64287, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Apenberg
authors.forename: M A
authors.initials: MA
authors.lastname: Freyberg
authors.forename: P
authors.initials: P
authors.lastname: Friedl
mesh_terms: D000818:Animals; D017209:Apoptosis; D019898:Autocrine Communication; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013314:Stress, Mechanical; D019014:fas Receptor / Q000502:physiology*
chemical_list: D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D019014:fas Receptor