Shear stress-dependent expression of apoptosis-regulating genes in endothelial cells.
Laminar shear stress exerts potent anti-apoptotic effects. Therefore, we analyzed the influence of laminar shear stress on the expression of apoptosis-regulating genes in human umbilical vein endothelial cells (HUVEC). Application of high levels of laminar shear stress (15 and 30 dyn/cm(2)) decreased the susceptibility of HUVEC to undergo apoptosis, whereas low shear stress (1 dyn/cm(2)) had no effect. These diminished signs of apoptosis were accompanied by a decreased mRNA expression of apoptosis-inducing Fas receptor. Furthermore, mRNA and protein expression of anti-apoptotic, soluble Fas isoform FasExo6Del and anti-apoptotic Bcl-x(L) were induced. Surprisingly, high shear stress also elevated mRNA and protein expression of pro-apoptotic Bak. The shear stress-induced up-regulation of Bcl-x(L) and Bak mRNA can be abrogated by inhibition of the endothelial NO synthase. We propose that altered expression of Bcl-x(L) and the Fas system is involved in the protective effect of laminar shear stress against apoptosis in human endothelial cells.
Bartling
B
B
Clinic for Heart and Thoracic Surgery, Institute of Pathophysiology, Halle (Saale), D-06097, Germany.
Tostlebe
H
H
Darmer
D
D
Holtz
J
J
Silber
R E
RE
Morawietz
H
H
D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000502:physiology*; D019254:Genes, bcl-2; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013314:Stress, Mechanical; D014158:Transcription, Genetic; D014471:Umbilical Veins; D019014:fas Receptor / Q000235:genetics
D017931:DNA Primers; D020033:Protein Isoforms; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D019014:fas Receptor