Bartling B, Tostlebe H, Darmer D, Holtz J, Silber R E, Morawietz H
Clinic for Heart and Thoracic Surgery, Institute of Pathophysiology, Halle (Saale), D-06097, Germany.
Biochem Biophys Res Commun. 2000 Nov 30;278(3):740-6. 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/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.
层流切应力具有强大的抗凋亡作用。因此，我们分析了层流切应力对人脐静脉内皮细胞（HUVEC）中凋亡调节基因表达的影响。施加高水平的层流切应力（15和30达因/平方厘米）可降低HUVEC发生凋亡的易感性，而低切应力（1达因/平方厘米）则无此作用。这些凋亡迹象的减弱伴随着凋亡诱导因子Fas受体mRNA表达的降低。此外，抗凋亡的可溶性Fas异构体FasExo6Del和抗凋亡蛋白Bcl-x(L)的mRNA及蛋白表达均被诱导。令人惊讶的是，高切应力还能提高促凋亡蛋白Bak的mRNA及蛋白表达。内皮型一氧化氮合酶的抑制可消除切应力诱导的Bcl-x(L)和Bak mRNA的上调。我们认为，Bcl-x(L)和Fas系统表达的改变参与了层流切应力对人内皮细胞凋亡的保护作用。
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