Yang Hui-ling, Xu Yang-yan, DU Li-fen, Liu Chang-hui, Zhao Qiang, Wei Wu-jie, You Yong, Quan Zhi-hua
Institute of Clinical Medicine, First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, China.
Chin Med J (Engl). 2008 Jan 20;121(2):112-7.
Scavenger receptor that binds phosphatidylserine and oxidized lipoprotein/CXC chemokine ligand 16 (SR-PSOX/CXCL16) promotes foam cell formation through the tumor necrosis factor (TNF)-alpha mediated mechanism. Because chemokine CXCL16 could be expressed in atherosclerotic lesions and induce smooth muscle cell (SMC) proliferation, we presume that the monocyte SR-PSOX/CXCL16 detection in the patients' peripheral blood will be important for early diagnosis and prognosis of atherosclerosis (AS).
Enrolled in this study were 40 patients with acute coronary syndrome (ACS), including 20 patients with acute myocardial infarction (AMI) and 20 patients with unstable angina pectoris (UAP), and 20 normal controls. Monocytes in the peripheral blood were isolated, and the changes of expression of CXCL16/SR-PSOX mRNA were compared using reverse transcription-polymerase chain reaction (RT-PCR), with beta-actin as internal control. We compared the expression of CXCL16/SR-PSOX in the ACS subgroups, using Western-blot to analyze protein expression levels. Tissue sections were made from biopsy specimens taken from patients with infective endocarditis, liver cirrhosis, and lung cancer as well as normal controls. And the expression of CXCL16/SR-PSOX was analyzed with a confocal microscope.
The expression of CXCL16/SR-PSOX mRNA and protein in the monocytes of peripheral blood was significantly higher in ACS patients than in normal controls (P < 0.05); however, there was no significant difference in CXCL16/SR-PSOX expression between UAP group and AMI group (P > 0.05). Immunofluorescence showed that there were low expression of SR-PSOX in normal vascular endothelial cells and enhanced expression in every layer of the infected vessels, while spreading from endothelial cells to surrounding tissues as infection worsens. Confocal microscopy showed that the expression of SR-PSOX was enhanced in the infiltrated lymphocytes in liver cirrhosis, and that the expression level was proportionate to the degree of inflammation in the portal hepatis and folia.
The expression of CXCL16/SR-PSOX in the monocytes of peripheral blood was significantly higher in ACS patients than in the controls. CXCL16/SR-PSOX-mediated inflammation may contribute to the pathogenesis of ACS, and CXCL16 may play an important role in the pathogenesis and development of AS in humans.
结合磷脂酰丝氨酸和氧化脂蛋白/CXC趋化因子配体16的清道夫受体（SR-PSOX/CXCL16）通过肿瘤坏死因子（TNF）-α介导的机制促进泡沫细胞形成。由于趋化因子CXCL16可在动脉粥样硬化病变中表达并诱导平滑肌细胞（SMC）增殖，我们推测检测患者外周血中的单核细胞SR-PSOX/CXCL16对动脉粥样硬化（AS）的早期诊断和预后具有重要意义。
本研究纳入40例急性冠状动脉综合征（ACS）患者，其中包括20例急性心肌梗死（AMI）患者和20例不稳定型心绞痛（UAP）患者，以及20例正常对照者。分离外周血中的单核细胞，以β-肌动蛋白为内参，采用逆转录-聚合酶链反应（RT-PCR）比较CXCL16/SR-PSOX mRNA表达的变化。我们比较了ACS各亚组中CXCL16/SR-PSOX的表达情况，采用蛋白质印迹法分析蛋白质表达水平。取感染性心内膜炎、肝硬化和肺癌患者以及正常对照者的活检标本制作组织切片，并用共聚焦显微镜分析CXCL16/SR-PSOX的表达。
ACS患者外周血单核细胞中CXCL16/SR-PSOX mRNA和蛋白质的表达显著高于正常对照者（P < 0.05）；然而，UAP组和AMI组之间CXCL16/SR-PSOX的表达无显著差异（P > 0.05）。免疫荧光显示，正常血管内皮细胞中SR-PSOX表达较低，而在感染血管的各层中表达增强，且随着感染加重从内皮细胞向周围组织扩散。共聚焦显微镜显示，肝硬化浸润淋巴细胞中SR-PSOX的表达增强，且表达水平与肝门区和小叶的炎症程度成正比。
ACS患者外周血单核细胞中CXCL16/SR-PSOX的表达显著高于对照者。CXCL16/SR-PSOX介导的炎症可能参与了ACS的发病机制，且CXCL16可能在人类AS的发病机制和发展中起重要作用。
