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论文 |
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| 论文题目: |
Mitochondrial DNA-LL-37 Complex Promotes Atherosclerosis by Escaping from Autophagic Recognition |
| 作者: |
Zhiye Zhang; Ping Meng; Yajun Han; Chuanbin Shen; Bowen Li; Md Abdul Hakim; Xuguang Zhang; Qiumin Lu; Mingqiang Rong; Ren Lai* |
| 联系作者: |
rlai@mail.kiz.ac.cn |
| 发表年度: |
2015 |
| DOI: |
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| 摘要: |
Atherosclerosis is a chronic inflammatory disease of arterial wall. Mitochondrial DNA (mtDNA) and human antimicrobial peptide LL-37 (Cramp in mice) are involved in atherosclerosis. Recently, mtDNA has been found to escape from autophagy and cause inflammation. Normally, mtDNA as an inflammatogenic factor cannot escape from autophagy and degradation by DNase II. In this study, we found elevated amounts of LL37-mtDNA complex in atherosclerotic plasma and plaques. The complex was resistant to DNase II degradation and escaped from autophagic recognition, leading to activation of Toll-like receptor 9 (TLR9)-mediated inflammatory responses. Mouse model studies indicated that Cramp-mtDNA complex aggravated atherosclerotic lesion formation in apolipoprotein E-deficient mice and antibody treatment against the complex alleviated the lesion. These findings suggest that the LL-37-mtDNA complex acts as a key mediator of atherosclerosis formation, and thus represents a promising therapeutic target. |
| 刊物名称: |
Immunity |
| 论文出处: |
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| 影响因子: |
21.561 (2014) |
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