Molenaar R, Visser W J, Verkerk A, Koster J F, Jongkind J F
Department of Cell Biology and Genetics, Erasmus University Rotterdam, The Netherlands.
Atherosclerosis. 1989 Apr;76(2-3):193-202. doi: 10.1016/0021-9150(89)90103-2.
Adherence of monocytes to the endothelium is an early event in atherogenesis. Changes in the endothelium are probably involved in this process. We have investigated the influence of peroxidative stress and in vitro ageing of endothelial cells on the subsequent adherence of monocytes using an in vitro system. Treatment of young human umbilical vein endothelial cells (HUVEC) with 60 microM cumene hydroperoxide (Chp) resulted in a 2.1-fold increase in monocyte adherence. This increase was not dependent on de novo synthesis of membrane antigens. No such increase upon Chp treatment was observed using young human umbilical artery endothelial cells (HUAEC) and in vitro aged HUVEC and HUAEC. As compared with "young" HUVEC, a higher spontaneous adherence of monocytes to "young" HUAEC (1.8 times), "aged" HUVEC (2.5 times) and "aged" HUAEC (2.7 times) was observed. Furthermore, fibroblasts showed an about 3 times higher monocyte adherence, whereas an 8 times higher adherence was observed to endothelial extracellular matrix. These data suggest that the spontaneous monocyte adherence to "young", intact endothelium can be increased by peroxidative damaging and by ageing of the endothelial cells. A denudation and subsequent exposure of the extracellular matrix may further stimulate this process. The possible physiological vector for endothelial peroxidation is discussed.
单核细胞与内皮细胞的黏附是动脉粥样硬化发生过程中的早期事件。内皮细胞的变化可能参与了这一过程。我们使用体外系统研究了过氧化应激和内皮细胞体外老化对随后单核细胞黏附的影响。用60微摩尔的氢过氧化异丙苯(Chp)处理年轻的人脐静脉内皮细胞(HUVEC),导致单核细胞黏附增加2.1倍。这种增加不依赖于膜抗原的从头合成。使用年轻的人脐动脉内皮细胞(HUAEC)以及体外老化的HUVEC和HUAEC,在Chp处理后未观察到这种增加。与“年轻”的HUVEC相比,观察到单核细胞对“年轻”的HUAEC(1.8倍)、“老化”的HUVEC(2.5倍)和“老化”的HUAEC(2.7倍)的自发黏附更高。此外,成纤维细胞显示单核细胞黏附高出约3倍,而对内皮细胞外基质的黏附则高出8倍。这些数据表明,过氧化损伤和内皮细胞老化可增加单核细胞对“年轻”、完整内皮的自发黏附。细胞外基质的剥脱及随后的暴露可能会进一步刺激这一过程。文中讨论了内皮过氧化可能的生理介质。