Zhao Kai, Xu Xing Sheng, Meng Xiao, Li Yu Lan, Li Ji Fu, Chen Wen Qiang
aDepartment of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital of Shandong University bThe School of Medicine, Shandong University, Jinan, People's Republic of China.
Coron Artery Dis. 2013 Dec;24(8):651-6. doi: 10.1097/MCA.0000000000000035.
The aim of this study was to determine whether autophagy of monocytes attenuates the vulnerability of atherosclerotic plaques.
The study group comprised 50 patients with stable angina pectoris (SAP), 50 patients with unstable angina pectoris (UAP), 40 patients with acute myocardial infarction (AMI), and 30 patients without coronary artery disease (control). Peripheral blood monocytes (PBMs) were isolated and the expression levels of the proteins beclin-1 and light chain 3 (LC3) (autophagy-specific proteins) in the PBMs were analyzed by western blot. A laser scanning confocal microscope was used to determine the levels of LC3 in the PBMs.
Western blot analysis revealed that the expression of beclin-1 and LC3 was significantly lower in acute coronary syndrome patients than in the SAP and control groups (P<0.05). Among the acute coronary syndrome patients, the expression level of beclin-1 and LC3 in the AMI group was significantly decreased compared with that in the UAP group (P<0.05). However, there was no statistical difference between the SAP group and the control group. The results of immunofluorescence assays showed that the fluorescence intensity of LC3 in the PBMs of AMI patients was significantly lower than that in those of UAP patients (P<0.05), which was also significantly decreased compared with that in those of SAP patients and the control group (P<0.05). Expression levels of beclin 1 in the UAP and AMI groups had a negative linear correlation with C-reactive protein levels (r=-0.531, P<0.05; r=-0.589, P<0.05, respectively).
Autophagy of PBMs is involved in the pathogenesis of plaque vulnerability and subsequent plaque rupture. Enhancing the autophagy of PBMs may be a new therapeutic target for stabilizing atherosclerotic plaques.
本研究旨在确定单核细胞自噬是否会降低动脉粥样硬化斑块的易损性。
研究组包括50例稳定型心绞痛（SAP）患者、50例不稳定型心绞痛（UAP）患者、40例急性心肌梗死（AMI）患者和30例无冠状动脉疾病的患者（对照组）。分离外周血单核细胞（PBMs），采用蛋白质免疫印迹法分析PBMs中自噬特异性蛋白贝林1（beclin-1）和微管相关蛋白轻链3（LC3）的表达水平。使用激光扫描共聚焦显微镜测定PBMs中LC3的水平。
蛋白质免疫印迹分析显示，急性冠状动脉综合征患者中beclin-1和LC3的表达明显低于SAP组和对照组（P<0.05）。在急性冠状动脉综合征患者中，AMI组beclin-1和LC3的表达水平与UAP组相比明显降低（P<0.05）。然而，SAP组和对照组之间无统计学差异。免疫荧光分析结果显示，AMI患者PBMs中LC3的荧光强度明显低于UAP患者（P<0.05），与SAP患者和对照组相比也明显降低（P<0.05）。UAP组和AMI组中beclin 1的表达水平与C反应蛋白水平呈负线性相关（r分别为-0.531，P<0.05；-0.589，P<0.05）。
PBMs自噬参与了斑块易损性及随后斑块破裂的发病机制。增强PBMs自噬可能是稳定动脉粥样硬化斑块的一个新的治疗靶点。
