Shen Y, Rattan V, Sultana C, Kalra V K
Department of Biochemistry and Molecular Biology, University of Southern California School of Medicine, Los Angeles, 90033, USA.
Am J Physiol. 1996 May;270(5 Pt 2):H1624-33. doi: 10.1152/ajpheart.1996.270.5.H1624.
Cigarette smoking is clearly linked with increased incidence of atherosclerosis and cardiovascular disease. The adherence of blood monocytes to the endothelium, followed by their migration beneath the endothelium, are initiating events in the formation of foam cells, promoting atherogenesis. We show that cigarette smoke condensate (CSC)-induced surface expression of a subset of cell adhesion molecules (CAM) [intercellular adhesion molecule 1 (ICAM-1), endothelial leukocyte adhesion molecule 1 (ELAM-1), and vascular cell adhesion molecule 1 (VCAM-1)] in human umbilical vein endothelial cells (HUVEC) is associated with an increase in the binding activity of nuclear transcription factor NF-kappa B to the consensus motif common to the CAM genes. Furthermore, CSC (25 microgram/ml) both increases the rate of transendothelial migration of vitamin D3-differentiated monocyte-like cells across the HUVEC monolayer by 200% and causes an approximately 10-fold increases in the phosphorylation of platelet endothelial CAM (PECAM-1), an adhesion molecule located at intercellular junctions and involved in endothelial cell-cell adhesion. Our results show that CSC-induced activation of protein kinase C in endothelial cells initiates a signaling pathways, leading to heightened binding of NF-kappa B to specific DNA sequences, which in turn increases surface expression of the subset of CAMs. Furthermore, our studies demonstrate a link between the phosphorylation of PECAM-1 and the migration of blood monocytes across vascular endothelium.
吸烟与动脉粥样硬化和心血管疾病发病率的增加明显相关。血液单核细胞黏附于内皮，随后迁移至内皮下方，是泡沫细胞形成的起始事件，促进动脉粥样硬化的发生。我们发现，香烟烟雾冷凝物（CSC）诱导人脐静脉内皮细胞（HUVEC）中细胞黏附分子（CAM）子集[细胞间黏附分子1（ICAM-1）、内皮白细胞黏附分子1（ELAM-1）和血管细胞黏附分子1（VCAM-1）]的表面表达，这与核转录因子NF-κB与CAM基因共有的共有基序的结合活性增加有关。此外，CSC（25微克/毫升）使经维生素D3分化的单核细胞样细胞跨HUVEC单层的跨内皮迁移率提高200%，并使血小板内皮CAM（PECAM-1）的磷酸化增加约10倍，PECAM-1是一种位于细胞间连接处并参与内皮细胞间黏附的黏附分子。我们的结果表明，CSC诱导内皮细胞中蛋白激酶C的激活启动了一条信号通路，导致NF-κB与特定DNA序列的结合增强，进而增加了CAM子集的表面表达。此外，我们的研究证明了PECAM-1的磷酸化与血液单核细胞跨血管内皮迁移之间的联系。
