Cholesterol increases adhesion of monocytes to endothelium by moving adhesion molecules out of caveolae
Cholesterol increases adhesion of monocytes to endothelium by moving adhesion molecules out of caveolae
复制标题
胆固醇通过将粘附分子移出小凹来增加单核细胞与内皮的粘附
DOI：
10.1016/j.bbalip.2010.04.001
复制
发表时间：
2010-07-01
影响因子：
4.8
通讯作者：
Zhu, Yi
中科院分区：
文献类型：
--
作者：
Fu, Chenglai;He, Jinlong;Zhu, Yi
Caveolae及其结构蛋白Caveolin-1（Cav-1）在血管内皮细胞中含量丰富。我们研究了小窝是否参与单核细胞粘附到内皮细胞响应高胆固醇血症和炎症的协同作用。胆固醇处理人脐静脉内皮细胞可增强内毒素脂多糖（LPS）诱导的单核细胞粘附。使用分离的小窝富集膜显示，细胞粘附分子（CAM），包括细胞间粘附分子-1（ICAM-1）和血管细胞粘附分子-1（VCAM-1），与Cav-1共定位于小窝。LPS可上调CAMs的表达，增加其共定位。胆固醇暴露降低CAMs的水平在小窝。免疫共沉淀和共聚焦显微镜显示ICAM-1与Cav-1相互作用。电镜下ICAM-1主要定位于细胞膜小窝。胆固醇暴露降低了这种相互作用，并将ICAM-1赶出了小窝。Cav-1的敲低降低了胆固醇和炎症的协同作用。在体内，ICAM-1和Cav-1共定位在ApoE（-/-）小鼠的主动脉内皮中低于野生型对照。Cav-1通过CAMs在小窝中的共定位来负调节单核细胞粘附，这受到胆固醇的干扰。因此，我们的研究提示了动脉粥样硬化形成中高胆固醇血症和炎症协同作用的分子基础。(C)2010爱思唯尔有限公司版权所有。
Caveolae and its structural protein caveolin-1 (Cav-1) are abundant in vascular endothelial cells (ECs). We examined whether caveolae are involved in monocyte adhesion to ECs responding to a synergy of hypercholesterolemia and inflammation. Treating human umbilical vein ECs with cholesterol enhanced endotoxin lipopolysaccharide (LPS)-induced monocyte adhesion. Use of isolated caveolae-enriched membranes revealed that cell adhesion molecules (CAMs), including intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), co-localized with Cav-1 in caveolae. LPS upregulated CAMs expression and increased the co-localization. Cholesterol exposure decreased the level of CAMs in the caveolae. Co-immunoprecipitation and confocal microscopy revealed that ICAM-1 interacted with Cav-1. Electron microscopy showed that ICAM-1 was mainly located in caveolae. Cholesterol exposure decreased this interaction and drove ICAM-1 out of caveolae. Knockdown of Cav-1 reduced the synergistic effects of cholesterol and inflammation. In vivo, ICAM-1 and Cav-1 co-localization was lower in the aortic endothelium of ApoE(-/-) mice than in that of wild-type controls. Cav-1 negatively regulates monocyte adhesion by the co-localization of CAMs in caveolae, which is disturbed by cholesterol. Thus, our study suggests a molecular basis underlying the synergistic effects of hypercholesterolemia and inflammation in atherogenesis. (C) 2010 Elsevier B.V. All rights reserved.