Vascular bed origin dictates flow pattern regulation of endothelial adhesion molecule expression
Vascular bed origin dictates flow pattern regulation of endothelial adhesion molecule expression
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DOI：
10.1152/ajpheart.00403.2006
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发表时间：
2007-05-01
影响因子：
4.8
通讯作者：
Edelman, Elazer R.
中科院分区：
文献类型：
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作者：
Methe, Heiko;Balcells, Mercedes;Edelman, Elazer R.
内皮细胞表型明显不同，取决于功能和血管床的起源。差异可能解释了对病理条件的特定易感性。由于白细胞对活化内皮的粘附是一系列疾病的起始事件，我们比较了血管床特异性血流模式对人隐静脉（HSVEC）和冠状动脉内皮细胞（HCAEC）粘附分子表达的影响。在体外，当肿瘤坏死因子(TNF) α刺激的HSVEC暴露于冠状动脉血流而不是生理静脉血流时，免疫细胞的附着增加了1.6倍，比暴露于冠状动脉血流的细胞因子刺激的HCAEC的附着增加了1.9倍。与暴露于相同血流模式的HCAEC相比，暴露于冠状动脉血流的HSVEC上清液中可溶性e -选择素、VCAM-1和ICAM-1的浓度增加。静脉和冠状动脉血流均增加了tnf - α诱导的e -选择素和ICAM-I在HSVEC上的表达，但只有冠状动脉血流增加了VCAM-I的表达。与HSVEC形成鲜明对比的是，静脉和冠状动脉血流可减弱tnf α诱导的e-选择素和VCAM-1在HCAEC上的表达，而冠状动脉血流可进一步诱导细胞因子刺激的HCAEC上的ICAM-1表达。除了细胞因子诱导的ICAM-1外，冠状动脉血流暴露的HSVEC上的粘附分子表达超过HCAEC上的表达。因此，ICAM-I的表达涉及复杂的流动依赖性和非依赖性途径，在两种内皮细胞类型之间存在显著差异。有趣的是，kruppel样因子（KLF） 4在HCAEC和HSVEC中的过表达在静态条件下显著降低tnf α诱导的e -选择素和vcam -1的表达，而ICAM-1的表达保持不变。此外，两种流型均可诱导HCAEC和HSVEC中KLF2和KLF4的表达。静脉和冠状动脉血流对内皮粘附分子和转录因子表达的影响不同，这取决于血管的起源床。HSVEC和HCAEC之间的粘附分子表达和随后的免疫细胞粘附的差异可能导致对病理条件的不同易感性。
Endothelial cell phenotypes markedly differ, depending upon unction and vascular bed of origin. Differences might account for specific susceptibility to pathological conditions. As leukocyte adhesion to activated endothelium is the initiating event in a range of diseases, we compared the influence of vascular bed-specific flow patterns on adhesion molecule expression in human saphenous vein (HSVEC) and coronary artery endothelial cells (HCAEC). In vitro, immune cell attachment was increased 1.6-fold when tumor necrosis factor (TNF)-alpha-stimulated HSVEC were exposed to coronary artery flow in place of physiological venous flow and 1.9-fold higher compared with attachment to cytokine-stimulated HCAEC exposed to coronary artery flow. This was associated with increased concentrations Of Soluble E-selectin, VCAM-1, and ICAM-1 in supernatants of HSVEC exposed to coronary artery flow compared with HCAEC exposed to the same flow pattern. Venous and coronary artery flow both increased TNF-alpha-induced E-selectin and ICAM-I expression on HSVEC, but only coronary artery flow increased VCAM-I expression. In marked contrast to HSVEC, venous and coronary artery flow attenuated TNF-alpha-induced E-selectin and VCAM-1 expression on HCAEC, whereas coronary artery flow further induced ICAM-1 on cytokine-stimulated HCAEC. With the exception of cytokine-induced ICAM-1, adhesion molecule expression on HSVEC exposed to coronary artery flow exceeded expression on HCAEC. Thus ICAM-I expression involves complex flow-dependent and -independent pathways with marked dissimilarities between the two endothelial cell types studied. Interestingly, Kruppel-like factor (KLF) 4 overexpression in HCAEC and HSVEC significantly reduced TNF-alpha-induced E-selectin and VCAM-I expression in static conditions, while ICAM-1 expression remained constant. Furthermore, both flow patterns induced KLF2 and KLF4 expression in HCAEC and HSVEC. Venous and coronary artery flow differentially influence endothelial adhesion molecule and transcription factor expression, depending on the vascular bed of origin. Differences in adhesion molecule expression and subsequent immune cell adhesion between HSVEC and HCAEC may contribute to different susceptibility to pathological conditions.