Decreased gene expression of LC3 in peripheral leucocytes of patients with coronary artery disease

Decreased gene expression of LC3 in peripheral leucocytes of patients with coronary artery disease
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冠心病患者外周血白细胞LC3基因表达降低

DOI:
10.1111/j.1365-2362.2011.02486.x
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发表时间:
2011-09-01
影响因子:
5.5
通讯作者:
Yan, Bo
Yan, Bo
中科院分区:
医学3区
文献类型:
--
作者:
Wu, Guanghua;Wei, Guanghe;Yan, Bo

文献摘要

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研究背景冠状动脉疾病(Coronary artery disease,CAD)是一种常见的多因素动脉疾病,主要由动脉粥样硬化引起。巨噬细胞、淋巴细胞和中性粒细胞与动脉粥样硬化斑块的发展有关。自噬是一种高度保守的细胞内清除长寿命蛋白质和细胞器的过程,具有多种病理生理作用。然而,在动脉粥样硬化和CAD.Materials和方法LC 3的外周血白细胞中的自噬的角色还没有被explored.LC3是自噬的标记基因,和LC 3-II,LC 3蛋白的缀合形式,是自噬体和自噬溶酶体的膜标记。本研究检测了146例冠心病患者和87例健康对照者外周血白细胞LC 3基因表达水平和LC 3-II蛋白水平。冠心病组LC 3-II蛋白水平明显低于正常对照组(P < 0.01)。多因素Logistic分析显示,LC 3基因表达水平降低与CAD密切相关。结论冠心病患者外周血白细胞中LC 3基因表达明显降低,提示自噬体形成减少。这些数据表明,循环中的白细胞自噬可能参与动脉粥样硬化和CAD的发病机制。
Background Coronary artery disease (CAD) is a common and multifactorial arterial disease that is mainly caused by atherosclerosis. Macrophages, lymphocytes and neutrophils have been implicated in atherosclerotic plaque development. Autophagy, a highly conserved cellular process for the removal of long-lived protein and organelles, plays a variety of pathophysiological roles. However, the roles of autophagy in peripheral leucocytes in atherosclerosis and CAD have not been explored.Materials and methods LC3 is a marker gene for autophagy, and LC3-II, a conjugated form of LC3 protein, is a membrane marker for autophagosome and autophagolysosomes. In this study, LC3 gene expression levels and LC3-II protein levels in peripheral leucocytes were measured in patients with CAD (n = 146) and healthy controls (n = 87).Results In patients with CAD, LC3 gene expression levels in the peripheral leucocytes were significantly decreased compared with age-and sex-matched healthy controls (P < 0.01). LC3-II protein levels were also significantly decreased in patients with CAD (P < 0.01). Multivariate logistic analyses showed that decreased LC3 gene expression levels were strongly associated with CAD. There were no differences in LC3 transcripts and LC3-II protein levels between subgroups of patients with CAD.Conclusions LC3 gene expression in the peripheral leucocytes was significantly decreased in patients with CAD, indicating that autophagosome formation is decreased. These data suggest that autophagy in circulating leucocytes may be involved in the pathogenesis of atherosclerosis and CAD.