title: Identification of a danger-associated peptide from apolipoprotein B100 (ApoBDS-1) that triggers innate proatherogenic responses.
abstract: BACKGROUND
  Subendothelial deposited low-density lipoprotein particles are a known inflammatory factor in atherosclerosis. However, the causal components derived from low-density lipoprotein are still poorly defined. Apolipoprotein B100 (ApoB100) is the unexchangeable protein component of low-density lipoprotein, and the progression of atherosclerosis is associated with immune responses to ApoB100-derived peptides. In this study, we analyzed the proinflammatory activity of ApoB100 peptides in atherosclerosis.
  
  
  RESULTS
  By screening a peptide library of ApoB100, we identified a distinct native peptide referred to as ApoB100 danger-associated signal 1 (ApoBDS-1), which shows sequence-specific bioactivity in stimulation of interleukin-8, CCL2, and interleukin-6. ApoBDS-1 activates mitogen-activated protein kinase and calcium signaling, thereby effecting the expression of interleukin-8 in innate immune cells. Ex vivo stimulation of carotid plaques with ApoBDS-1 enhances interleukin-8 and prostaglandin E₂ release. Furthermore, we demonstrated that ApoBDS-1-positive peptide fragments are present in atherosclerotic lesions using immunoassays and that low-molecular-weight fractions isolated from plaque show ApoBDS-1 activity inducing interleukin-8 production.
  
  
  CONCLUSIONS
  Our data show that ApoBDS-1 is a previously unrecognized peptide with robust proinflammatory activity, contributing to the disease-promoting effects of low-density lipoprotein in the pathogenesis of atherosclerosis.
authors: Center for Molecular Medicine, Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors: Daniel F J
authors: DF
authors: Ketelhuth
authors: Francisco J O
authors: FJ
authors: Rios
authors: Yajuan
authors: Y
authors: Wang
authors: Huiqing
authors: H
authors: Liu
authors: Maria E
authors: ME
authors: Johansson
authors: Gunilla N
authors: GN
authors: Fredrikson
authors: Ulf
authors: U
authors: Hedin
authors: Magnus
authors: M
authors: Gidlund
authors: Jan
authors: J
authors: Nilsson
authors: Göran K
authors: GK
authors: Hansson
authors: Zhong-Qun
authors: ZQ
authors: Yan
mesh_terms: D053299:Apolipoprotein B-100 / Q000502:physiology*; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology*; D002118:Calcium / Q000502:physiology; D002340:Carotid Artery Diseases / Q000473:pathology / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology; D016209:Interleukin-8 / Q000502:physiology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D010455:Peptides / Q000502:physiology*; D058226:Plaque, Atherosclerotic / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: C569471:APOB protein, human; D053299:Apolipoprotein B-100; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; D010455:Peptides; D020929:Mitogen-Activated Protein Kinase Kinases; D002118:Calcium