Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
Arterioscler Thromb Vasc Biol. 2011 Jan;31(1):160-6. doi: 10.1161/ATVBAHA.110.215434. Epub 2010 Oct 28.
Atherosclerosis is associated with monocyte adhesion to the arterial wall that involves integrin activation and emigration across inflamed endothelium. Involvement of β(2)-integrin CD11c/CD18 in atherogenesis was recently shown in dyslipidemic mice, which motivates our study of its inflammatory function during hypertriglyceridemia in humans.
Flow cytometry of blood from healthy subjects fed a standardized high-fat meal revealed that at 3.5 hours postprandial, monocyte CD11c surface expression was elevated, and the extent of upregulation correlated with blood triglycerides. Monocytes from postprandial blood exhibited an increased light scatter profile, which correlated with elevated CD11c expression and uptake of lipid particles. Purified monocytes internalized triglyceride-rich lipoproteins isolated from postprandial blood through low-density lipoprotein-receptor-related protein-1, and this also elicited CD11c upregulation. Laboratory-on-a-chip analysis of whole blood showed that monocyte arrest on a vascular cell adhesion molecule-1 (VCAM-1) substrate under shear flow was elevated at 3.5 hours and correlated with blood triglyceride and CD11c expression. At 7 hours postprandial, blood triglycerides decreased and monocyte CD11c expression and arrest on VCAM-1 returned to fasting levels.
During hypertriglyceridemia, monocytes internalize lipids, upregulate CD11c, and increase adhesion to VCAM-1. These data suggest that analysis of monocyte inflammation may provide an additional framework for evaluating individual susceptibility to cardiovascular disease.
动脉粥样硬化与单核细胞黏附于动脉壁有关，涉及整合素的激活和穿过炎症内皮细胞的迁移。β(2)-整合素 CD11c/CD18 在血脂异常小鼠的动脉粥样硬化形成中起作用，这促使我们研究其在人类高甘油三酯血症中的炎症功能。
对健康受试者进食标准化高脂肪餐后的血液进行流式细胞术分析显示，餐后 3.5 小时，单核细胞 CD11c 表面表达增加，上调程度与血甘油三酯水平相关。餐后血液中的单核细胞表现出更高的光散射特征，这与 CD11c 表达的上调和脂质颗粒的摄取相关。从餐后血液中分离的富含甘油三酯的脂蛋白通过低密度脂蛋白受体相关蛋白-1被纯化的单核细胞内化，这也引起 CD11c 的上调。全血芯片分析显示，在剪切流下，单核细胞在血管细胞黏附分子-1（VCAM-1）底物上的阻滞在 3.5 小时时升高，并与血甘油三酯和 CD11c 表达相关。在餐后 7 小时时，血甘油三酯降低，单核细胞 CD11c 表达和在 VCAM-1 上的阻滞恢复到空腹水平。
在高甘油三酯血症期间，单核细胞摄取脂质，上调 CD11c，并增加与 VCAM-1 的黏附。这些数据表明，单核细胞炎症的分析可能为评估个体对心血管疾病的易感性提供一个额外的框架。
