Chen Youqin, Chen Huaiqing, Zhang Wensheng, Liu Xiaoheng, Lei Song, Mao Yongqiu
Institute of Biomedical Engineering, West China Medical Center, Sichuan University, Chengdu 610041.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2002 Dec;19(4):648-51, 672.
Extensive monocyte recruitment is an early phenomenon associated with the development of atherosclerotic lesion. Although the molecular mechanisms are not completely understood, monocyte recruitment into these early lesions may involve changes in endothelial adhesion for monocyte, in which adhesion molecules expressed by endothelial cell play an active role. In vivo, the function of endothelial cells is not only affected by the chemical factors, but also by the mechanical factors. The purpose of this article was to investigate the induction of adhesion molecules expression by synergistic effects of Lysophosphatidylcholine (Lyso-PC) and shear stress in cultured human umbilical vein endothelial cells (HUVEC). The surface expression of ICAM-1, VCAM-1 and E-selectin on HUVEC induced by Lyso-PC(30 micrograms/ml) and shear stress(2.23, 4.20 dyne/cm2) were analyzed using flow cytometry. The results showed that: Compared with what were simultaneously exposed to shear stress and Lyso-PC, activating the cells with Lyso-PC prior to shear stress, or pre-conditioning the cells exposed shear stress prior to Lyso-PC incubation, a significantly higher expression of ICAM-1 and VCAM-1(P < 0.05) was resulted. HUVEC were exposed to shear stress and Lyso-PC at the same time or treated with each agonist alone, E-selectin expression was not significantly different from the control group. However, a sequential action of the two stimuli significantly increased E-selectin expression(P < 0.05). We concluded that: a sequential action of the shear stress and Lyso-PC induced an even greater expression of ICAM-1 and VCAM-1, thus it could be understood that the flows-hear stress in combination with endothelial activated by chemical factors may increase the ability of endothelial cells to recruit leukocytes even under the mechanical environment unfavorable for cell adhesion.
大量单核细胞募集是动脉粥样硬化病变发展相关的早期现象。尽管分子机制尚未完全明确,但单核细胞募集到这些早期病变中可能涉及单核细胞在内皮的黏附变化,其中内皮细胞表达的黏附分子发挥着积极作用。在体内,内皮细胞的功能不仅受化学因子影响,还受机械因子影响。本文旨在研究溶血磷脂酰胆碱(Lyso-PC)与剪切应力协同作用对培养的人脐静脉内皮细胞(HUVEC)中黏附分子表达的诱导作用。采用流式细胞术分析Lyso-PC(30微克/毫升)和剪切应力(2.23、4.20达因/平方厘米)诱导的HUVEC表面ICAM-1、VCAM-1和E-选择素的表达。结果显示:与同时暴露于剪切应力和Lyso-PC的情况相比,在剪切应力之前先用Lyso-PC激活细胞,或在Lyso-PC孵育之前对暴露于剪切应力的细胞进行预处理,会导致ICAM-1和VCAM-1表达显著升高(P<0.05)。HUVEC同时暴露于剪切应力和Lyso-PC或单独用每种激动剂处理时,E-选择素表达与对照组无显著差异。然而,两种刺激的顺序作用显著增加了E-选择素表达(P<0.05)。我们得出结论:剪切应力和Lyso-PC的顺序作用诱导了更高的ICAM-1和VCAM-1表达,因此可以理解,血流剪切应力与化学因子激活的内皮相结合,即使在不利于细胞黏附的机械环境下,也可能增加内皮细胞募集白细胞的能力。