Alterations of autophagic-lysosomal system in the peripheral leukocytes of patients with myocardial infarction.
Alterations of autophagic-lysosomal system in the peripheral leukocytes of patients with myocardial infarction.
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DOI：
10.1016/j.cca.2011.05.002
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发表时间：
2011-08
期刊：
影响因子：
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通讯作者：
Guanghua Wu;Lixin Liu;Jian Huang;S. Pang;Guanghe Wei;Yinghua Cui;B. Yan
中科院分区：
文献类型：
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作者：
Guanghua Wu;Lixin Liu;Jian Huang;S. Pang;Guanghe Wei;Yinghua Cui;B. Yan
研究背景心肌梗死（MI）是一种常见的多因素疾病。迄今为止，因果基因和潜在机制仍然很大程度上未知。自噬-溶酶体系统是细胞中高度保守的降解过程，与脂质代谢有关。在本研究中，我们探讨了急性心肌梗死患者自噬-溶酶体系统的变化。方法通过RT-PCR和蛋白质印迹分析在转录和蛋白水平上检测心肌梗死患者外周白细胞中溶酶体标记基因溶酶体相关膜蛋白2（LAMP-2）和自噬标记基因微管相关蛋白1轻链3（LC3）的基因表达。结果与年龄和性别匹配的健康对照者 (n = 146) 相比，MI 患者 (n = 81) 的 LC3 基因表达和 LC3-II 蛋白（LC3 蛋白的裂解形式）水平显着降低。 LAMP-2基因表达和蛋白水平显着增加。 LC3 基因表达水平降低（OR，2.150，95%CI，1.050–4.405，P = 0.036）或 LAMP-2 基因表达水平升高（OR，3.317，95%CI，1.588–6.931，P < 0.001）与 MI 相关。结论我们的研究结果表明，MI 的外周白细胞中患者自噬活性降低，溶酶体积累增加，这可能有助于 MI 的发病机制。有必要对自噬溶酶体基因进行进一步的遗传分析。
BackgroundMyocardial infarction (MI) is a common and multifactorial disease. To date, causal genes and underlying mechanisms remain largely unknown. Autophagic–lysosomal system, a highly conserved degradative process in cells, has been implicated in lipid metabolism. In this study, we explored the alterations of the autophagic–lysosomal system in patients with acute MI.MethodsGene expression of lysosomal associated membrane protein 2 (LAMP-2), a lysosomal marker gene, and microtubule-associated protein 1 light chain 3 (LC3), an autophagy marker gene, in the peripheral leukocytes of MI patients were examined at transcription and protein levels by RT-PCR assay and western blot analysis, respectively.ResultsCompared to age- and sex-matched healthy controls (n = 146), levels of LC3 gene expression and LC3-II protein, a cleaved form of LC3 protein, were significantly decreased in MI patients (n = 81). LAMP-2 gene expression and protein levels were significantly increased. Decreased LC3 gene expression (OR, 2.150, 95%CI, 1.050–4.405, P = 0.036) or increased LAMP-2 gene expression (OR, 3.317, 95%CI, 1.588–6.931, P < 0.001) levels were associated with MI.ConclusionsOur findings indicated that in the peripheral leukocytes of MI patients, autophagy activity is reduced and lysosomal accumulation is increased, which may contribute to the MI pathogenesis. Further genetic analyses of autophagic–lysosomal genes are warranted.