Linsel-Nitschke Patrick, Jansen Henning, Aherrarhou Zouhair, Belz Stefanie, Mayer Björn, Lieb Wolfgang, Huber Fritz, Kremer Werner, Kalbitzer Hans-Robert, Erdmann Jeanette, Schunkert Heribert
Department of Medicine, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
Lipids Health Dis. 2009 Apr 6;8:14. doi: 10.1186/1476-511X-8-14.
Studies in patients with low HDL have suggested that impaired cellular cholesterol efflux is a heritable phenotype increasing atherosclerosis risk. Less is known about the association of macrophage cholesterol efflux with lipid profiles and CAD risk in normolipidemic subjects. We have therefore measured macrophage cholesterol efflux in 142 normolipidemic subjects undergoing coronary angiography.
Monocytes isolated from blood samples of patients scheduled for cardiac catheterization were differentiated into macrophages over seven days. Isotopic cholesterol efflux to exogenously added apolipoprotein A-I and HDL2 was measured. Quantitative cholesterol efflux from macrophages was correlated with lipoprotein subclass distribution in plasma from the same individuals measured by NMR-spectroscopy of lipids and with the extent of coronary artery disease seen on coronary angiography.
Macrophage cholesterol efflux was positively correlated with particle concentration of smaller HDL and LDL particles but not with total plasma concentrations of HDL or LDL-cholesterol. We observed an inverse relationship between macrophage cholesterol efflux and the concentration of larger and triglyceride rich particles (VLDL, chylomicrons). Subjects with significant stenosis on coronary angiography had lower cholesterol efflux from macrophages compared to individuals without significant stenosis (adjusted p = 0.02).
Macrophage cholesterol efflux is inversely correlated with lipoprotein particle size and risk of CAD.
对高密度脂蛋白（HDL）水平较低患者的研究表明，细胞胆固醇流出受损是一种可遗传的表型，会增加动脉粥样硬化风险。在血脂正常的受试者中，巨噬细胞胆固醇流出与血脂谱及冠心病风险之间的关联鲜为人知。因此，我们对142名接受冠状动脉造影的血脂正常受试者的巨噬细胞胆固醇流出情况进行了测量。
从计划进行心脏导管插入术患者的血样中分离出单核细胞，在7天内将其分化为巨噬细胞。测量向外源性添加的载脂蛋白A-I和HDL2的同位素胆固醇流出。巨噬细胞的定量胆固醇流出与通过脂质核磁共振光谱法测量的同一受试者血浆中的脂蛋白亚类分布以及冠状动脉造影所见的冠状动脉疾病程度相关。
巨噬细胞胆固醇流出与较小HDL和LDL颗粒的颗粒浓度呈正相关，但与HDL或LDL胆固醇的总血浆浓度无关。我们观察到巨噬细胞胆固醇流出与较大且富含甘油三酯的颗粒（极低密度脂蛋白、乳糜微粒）浓度之间呈负相关。与无明显狭窄的个体相比，冠状动脉造影有明显狭窄的受试者巨噬细胞的胆固醇流出较低（校正p = 0.02）。
巨噬细胞胆固醇流出与脂蛋白颗粒大小及冠心病风险呈负相关。
