Increased plasma levels of the soluble form of Fas ligand in patients with acute myocardial infarction and unstable angina pectoris.
Increased plasma levels of the soluble form of Fas ligand in patients with acute myocardial infarction and unstable angina pectoris.
复制标题
DOI：
10.1016/s0735-1097(01)01800-9
复制
发表时间：
2002-02
影响因子：
24
通讯作者：
M. Shimizu;K. Fukuo;S. Nagata;T. Suhara;M. Okuro;K. Fujii;Y. Higashino;M. Mogi;Y. Hatanaka;T. Ogihara
中科院分区：
文献类型：
--
作者：
M. Shimizu;K. Fukuo;S. Nagata;T. Suhara;M. Okuro;K. Fujii;Y. Higashino;M. Mogi;Y. Hatanaka;T. Ogihara
目的通过测定急性心肌梗死（AMI）合并稳定型和不稳定型心绞痛（AP）患者血浆中可溶性Fas配体（sFasL）的水平，探讨Fas/Fas配体系统是否参与急性心肌梗死（AMI）的发病机制。Fas配体（FasL）被金属蛋白酶从细胞膜上迅速切割，成为一种可溶性的细胞因子。Fas在包括心肌细胞在内的大多数细胞中表达，而FasL主要在巨噬细胞等炎症细胞中表达，巨噬细胞大量积聚在不稳定斑块中。方法AMI患者30例，不稳定AP患者10例，稳定AP患者10例，对照组30例。结果AMI合并不稳定AP患者入院时血浆sFasL水平明显高于对照组。时间过程研究显示，AMI患者经皮冠状动脉腔内成形术后血浆sFasL水平在3小时内迅速下降，然后再次上升，而稳定AP患者则没有。重要的是，冠状动脉窦的sFasL水平高于循环。此外，体外研究表明，AMI患者分离的单核细胞中FasL信使核糖核酸的表达上调，缺氧刺激分离的单核细胞释放sFasL。结论心肌梗死和AP不稳定患者中sFasL水平升高，提示Fas/FasL系统的激活可能在心肌梗死和急性冠状动脉综合征中起致病作用。
ObjectivesTo examine whether the Fas/Fas ligand system is involved in the pathogenesis of acute myocardial infarction (AMI), we measured the levels of the soluble form of the Fas ligand (sFasL) in the plasma of patients with AMI and stable or unstable angina pectoris (AP).BackgroundThe Fas ligand (FasL) is rapidly cleaved off by a metalloproteinase from the cell membrane to become a soluble form as a cytokine. Fas is expressed in most cells, including cardiomyocytes, whereas FasL is mainly expressed in inflammatory cells such as macrophages, which are greatly accumulated in unstable plaque.MethodsThirty patients with AMI, 10 patients with unstable AP, 10 patients with stable AP and 30 control subjects were enrolled in the present study.ResultsPlasma sFasL levels were significantly elevated on hospital admission in patients with AMI and unstable AP, compared with control subjects. Time-course studies revealed that plasma sFasL levels rapidly decreased within 3 h and then increased again after percutaneous transluminal coronary angioplasty in patients with AMI, but not in patients with stable AP. Importantly, the sFasL levels were higher in the coronary sinus than in the circulation. In addition, in vitro studies showed that the expression of FasL messenger ribonucleic acid was upregulated in mononuclear cells isolated from patients with AMI and that hypoxia stimulated the release of sFasL from isolated mononuclear cells.ConclusionsThis demonstration of elevated levels of sFasL in patients with AMI and unstable AP suggests that activation of the Fas/FasL system may play a pathogenic role in AMI and acute coronary syndromes.