Effect Of Shear Stress To The Apoptosis Of Endothelial Cells Induced By LPS

The luminal surface of the blood vessel and its endothelial surface are constantly exposed to hemodynamic shear stress. So, any change in blood flow could cause the change of endothelium. Atherosclerotic lesions long have been known to occur near vascular branching points. Study have identified in these predisposed areas, hemodynamic shear stress, the frictional force acting on the endothulial cell surface as a result of blood flow, is weaker than in protected regions. From the view of cellular rheology, we examined the influence of fluid shear stress on the metabolism, morphology, structure and function of endothelia cells in our previous research. It is first time for us to develop the research between shear stress and apoptosis. In this study, we stimulate the human umbilical venous endothelial cells (HUVEC) by LPS and apply different levels of fluid shear stress to them by a parallel plate flow chamber, then observe the change of apoptosis of endothelial cells by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL). We hope that our research can contribute to the signal transduction of apoptosis modulated by shear stress.First of all, we stimulate the HUVEC with LPS (50ug/ml) to observe the damage of cells. We find that LPS was able to induce apoptosis of HUVECs in a time - dependent fashion.On this condition, we exert two different levels of fluid shear stress (4 dyns/cm2and 15 dyns/cm2) to them by a parallel plate flowchamber and observe the change of apoptosis of endothelial cells by TUNEL. We demonstrate that high level shear stress can inhibit the apoptosis induced by LPS, whereas low level shear stress was less effective. With the previous relative research, we suppose that there was a common signal transduction pathway between shear stress and LPS. The inhibit effect of shear stress do not bring into play via increasing the level of bFGF. It may act directly on the ICE-like protease family or upstream of them in the signal transduction.At the same time, we investigate the change of IL-6 and IL~8 in perfusin medium duo to the atherosclerosis is a pathological process characterized by chronic inflammatory. The major method employed is radiation-iminunoassays. We measured IL-6 and IL~8 in the perfusion after applying shear stresses. The results of the experiment demonstrated the increase of IL-6 secretion by LPS can be inhibit by two different levels shear stress. Moreover, the inhibition effect was more obvious by high level stress than the low level shear stress. At the same Lime, we also found that the effect of shear stress on IL-8 is less effective than IL-6. These results deeply support the experiment of apoptosis. The inhibition of IL-6 by shear stress reduced the damage on HUVEC. However, this point could not be the primary cause for the inhibition effect of shear stresson apoptosis induced by LPS.This research provides data for understanding the mechanism of the contribution of hemodynamic forces to atherosclerosis.