title: Pathologically elevated cyclic hydrostatic pressure induces CD95-mediated apoptotic cell death in vascular endothelial cells.
abstract: We describe cyclic hydrostatic pressure of 200/100 mmHg with a frequency of 85/min as a hemodynamically relevant pathological condition enforcing apoptosis in endothelial cells (EC) after 24 h of treatment. This went along with an increase of CD95 and CD95L surface expression, shedding of CD95L into the supernatant, cleavage of caspase-3 and caspase-8, and elevated JNK-2, c-Jun, and CD95L mRNA expression. Furthermore, increased DNA-binding activity of the AP-1 transcription factor family members FRA-1 and c-Jun was observed. This activation was reduced by inhibition of JNK, which subsequently prevented elevated CD95L mRNA expression. Caspase inhibitors and a CD95L-neutralizing antibody also reduced EC apoptosis. Most of the pressure-induced events were most prominent at 24 and 48 h. However, after 48 h, the CD95/CD95L expression pattern switched back to CD95-/CD95L+ and the specific death rate decreased. Cyclic pathological hydrostatic pressure is a novel type of stress to EC that renders them susceptible to CD95/CD95L-mediated autoapoptosis and/or paracrine apoptosis accompanied by upregulation of intracellular molecules known to trigger both apoptosis and survival.
authors.affiliation: Institute of Pathology, University of Ulm, Ulm, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hasel
authors.forename: Susanne
authors.initials: S
authors.lastname: Dürr
authors.forename: Anke
authors.initials: A
authors.lastname: Bauer
authors.forename: Rene
authors.initials: R
authors.lastname: Heydrich
authors.forename: Silke
authors.initials: S
authors.lastname: Brüderlein
authors.forename: Tabe
authors.initials: T
authors.lastname: Tambi
authors.forename: Umesh
authors.initials: U
authors.lastname: Bhanot
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
mesh_terms: D001011:Aorta / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006801:Humans; D006874:Hydrostatic Pressure; D015151:Immunoblotting; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014471:Umbilical Veins / Q000166:cytology; D019014:fas Receptor / Q000096:biosynthesis*
chemical_list: D004791:Enzyme Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D014157:Transcription Factors; D019014:fas Receptor; D020169:Caspases