title: Shear stress inhibits apoptosis of human endothelial cells.
abstract: Physiological levels of shear stress alter the genetic program of cultured endothelial cells and reduce endothelial cell turnover in vivo. To test the hypothesis that shear stress interferes with programmed cell death, apoptosis was induced in human umbilical venous endothelial cells by growth factor withdrawal or incubation with tumor necrosis factor alpha (TNFalpha) for 18 h. Apoptosis was quantified by ELISA specific for histone-associated DNA fragments and confirmed by demonstrating the specific pattern of internucleosomal DNA fragmentation detected by electrophoresis and immunohistochemical staining. The TNFalpha (300 U/ml)-mediated increase in DNA fragmentation was completely abrogated by shear stress. Furthermore, shear stress dose-dependently reduced DNA fragmentation induced by growth factor withdrawal with maximal effect at 45 dyn/cm2. Inhibition of the CPP32-like proteases with Ac-DEVD-CHO (100 microM) revealed similar anti-apoptotic effects. In contrast, CPP32-independent induction of endothelial cell apoptosis by C2-ceramide (50 microM) was not prevented by shear stress. Thus, we propose that shear stress interferes with common cell death signal transduction involving the CPP32-like protease family and may contribute to endothelial cell integrity by inhibition of apoptosis.
authors.affiliation: Molecular Cardiology Group, Department of Internal Medicine IV, University of Frankfurt, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Dimmeler
authors.forename: J
authors.initials: J
authors.lastname: Haendeler
authors.forename: V
authors.initials: V
authors.lastname: Rippmann
authors.forename: M
authors.initials: M
authors.lastname: Nehls
authors.forename: A M
authors.initials: AM
authors.lastname: Zeiher
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D013312:Stress, Physiological; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D014409:Tumor Necrosis Factor-alpha