title: Mitochondrial DNA-LL-37 Complex Promotes Atherosclerosis by Escaping from Autophagic Recognition.
abstract: 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.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China; University of Chinese Academy of Sciences, Beijing 100009, China.
authors.forename: Zhiye
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Life Sciences College of Nanjing Agricultural University, 1st Weigang, Nanjing 210095, Jiangsu, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Meng
authors.affiliation: Life Sciences College of Nanjing Agricultural University, 1st Weigang, Nanjing 210095, Jiangsu, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Han
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China; University of Chinese Academy of Sciences, Beijing 100009, China.
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Shen
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China; University of Chinese Academy of Sciences, Beijing 100009, China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China; University of Chinese Academy of Sciences, Beijing 100009, China.
authors.forename: Md Abdul
authors.initials: MA
authors.lastname: Hakim
authors.affiliation: Major Cardiovascular Surgery, Kunming Yanan Hospital, Kunming 650051, Yunnan, China.
authors.forename: Xuguang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China.
authors.forename: Qiumin
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China.
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Rong
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China; Life Sciences College of Nanjing Agricultural University, 1st Weigang, Nanjing 210095, Jiangsu, China. Electronic address: rlai@mail.kiz.ac.cn.
authors.forename: Ren
authors.initials: R
authors.lastname: Lai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D001343:Autophagy / Q000502:physiology*; D054804:Cathelicidins / Q000378:metabolism*; D004272:DNA, Mitochondrial / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000378:metabolism* / Q000473:pathology
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D004272:DNA, Mitochondrial