Shear Stress-Dependent Expression of Apoptosis-Regulating Genes in Endothelial Cells

• Published in: Biochemical and biophysical research communications Vol. 278; no. 3; pp. 740 - 746
• Main Authors: Bartling, Babett, Tostlebe, Heike, Darmer, Dorothea, Holtz, Juergen, Silber, Rolf-Edgar, Morawietz, Henning
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.11.2000
• Subjects: apoptosis; Apoptosis - physiology; Bcl-2 family; Bcl-xL protein; Cells, Cultured; DNA Primers; Endothelium, Vascular - cytology; Endothelium, Vascular - physiology; Fas; Fas antigen; fas Receptor - genetics; Gene Deletion; Gene Expression Regulation - physiology; Genes, bcl-2; Humans; HUVEC; laminar shear stress; Protein Isoforms - genetics; Proto-Oncogene Proteins c-bcl-2 - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; shear stress; Stress, Mechanical; Transcription, Genetic; Umbilical Veins; apoptosis; Fas; HUVEC; shear stress; Bcl-2 family
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2000.3873

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/cm2) decreased the susceptibility of HUVEC to undergo apoptosis, whereas low shear stress (1 dyn/cm2) 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-xL were induced. Surprisingly, high shear stress also elevated mRNA and protein expression of pro-apoptotic Bak. The shear stress-induced up-regulation of Bcl-xL and Bak mRNA can be abrogated by inhibition of the endothelial NO synthase. We propose that altered expression of Bcl-xL and the Fas system is involved in the protective effect of laminar shear stress against apoptosis in human endothelial cells.