Carbamylated low-density lipoprotein induces monocyte adhesion to endothelial cells through intercellular adhesion molecule-1 and vascular cell adhesion molecule-1
Carbamylated low-density lipoprotein induces monocyte adhesion to endothelial cells through intercellular adhesion molecule-1 and vascular cell adhesion molecule-1
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DOI：
10.1161/01.atv.0000258795.75121.8a
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发表时间：
2007-04-01
影响因子：
8.7
通讯作者：
Basnakian, Alexei G.
中科院分区：
文献类型：
--
作者：
Apostolov, Eugene O.;Shah, Sudhir V.;Basnakian, Alexei G.
目的--氨甲酰化低密度脂蛋白（Carbamylated low-density lipoprotein，LDL）是人体血液中含量最丰富的一种修饰型LDL，近年来被证实与体外内皮细胞的动脉粥样硬化损伤和人体动脉粥样硬化有关。本研究旨在验证氨甲酰化低密度脂蛋白通过诱导单核细胞粘附内皮细胞的假设，并确定负责募集单核细胞的粘附分子。方法和结果-暴露于氨甲酰化低密度脂蛋白而不是天然低密度脂蛋白的人冠状动脉内皮细胞引起U937单核细胞粘附，并诱导细胞间粘附分子-1和血管细胞粘附分子-1。1粘附分子，如通过细胞酶联免疫吸附测定所测量的。通过siRNA沉默细胞间粘附分子-1或使用中和抗体抑制细胞间粘附分子-1导致单核细胞与内皮细胞的粘附减少。类似的沉默或中和单独的血管细胞粘附分子-1没有效果，但同时测试时显示有助于细胞间粘附分子-1。这些数据提供了细胞间粘附分子-1与血管细胞粘附分子-1协同作用对于通过氨甲酰化低密度脂蛋白的单核细胞粘附是必需的证据，体外激活人血管内皮细胞。
Objective - Carbamylated low-density lipoprotein (LDL), the most abundant modified LDL isoform in human blood, has been recently implicated in causing the atherosclerosis-prone injuries to endothelial cells in vitro and atherosclerosis in humans. This study was aimed at testing the hypothesis that carbamylated LDL acts via inducing monocyte adhesion to endothelial cells and determining the adhesion molecules responsible for the recruitment of monocytes.Methods and Results - Exposure of human coronary artery endothelial cells with carbamylated LDL but not native LDL caused U937 monocyte adhesion and the induction of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 adhesion molecules as measured by cell enzyme-linked immunosorbent assay. Silencing of intercellular adhesion molecule-1 by siRNA or its inhibition using neutralizing antibody resulted in decreased monocyte adhesion to the endothelial cells. Similar silencing or neutralizing of vascular cell adhesion molecule-1 alone did not have an effect but was shown to contribute to intercellular adhesion molecule-1 when tested simultaneously.Conclusions - Taken together, these data provide evidence that intercellular adhesion molecule-1 in cooperation with vascular cell adhesion molecule-1 are essential for monocyte adhesion by carbamylated low-density lipoprotein-activated human vascular endothelial cells in vitro.