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Identification of a Danger-Associated Peptide From Apolipoprotein B100 (ApoBDS-1) That Triggers Innate Proatherogenic Responses

Ketelhuth, Daniel F. J.; Rios, Francisco J. O.; Wang, Yajuan; Liu, Huiqing; Johansson, Maria E.; Nordin Fredrikson, Gunilla LU ; Hedin, Ulf; Gidlund, Magnus; Nilsson, Jan LU and Hansson, Goran K., et al. (2011) In Circulation 124(22). p.2433-2433
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. Methods and 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... (More)
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. Methods and 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 E(2) 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. (Circulation. 2011; 124: 2433-2443.) (Less)
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publication status
published
subject
keywords
apolipoprotein B100, atherosclerosis, innate immunity, macrophage, oxidized LDL
in
Circulation
volume
124
issue
22
pages
2433 - 2433
publisher
Lippincott Williams and Wilkins
external identifiers
  • wos:000298130700015
  • scopus:82355175118
ISSN
1524-4539
DOI
10.1161/CIRCULATIONAHA.111.051599
language
English
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yes
id
d01ebb68-2d10-4621-bcfa-5121f32d4669 (old id 2307030)
date added to LUP
2012-02-01 07:35:12
date last changed
2017-07-02 04:10:34
@article{d01ebb68-2d10-4621-bcfa-5121f32d4669,
  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. Methods and 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 E(2) 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. (Circulation. 2011; 124: 2433-2443.)},
  author       = {Ketelhuth, Daniel F. J. and Rios, Francisco J. O. and Wang, Yajuan and Liu, Huiqing and Johansson, Maria E. and Nordin Fredrikson, Gunilla and Hedin, Ulf and Gidlund, Magnus and Nilsson, Jan and Hansson, Goran K. and Yan, Zhong-qun},
  issn         = {1524-4539},
  keyword      = {apolipoprotein B100,atherosclerosis,innate immunity,macrophage,oxidized LDL},
  language     = {eng},
  number       = {22},
  pages        = {2433--2433},
  publisher    = {Lippincott Williams and Wilkins},
  series       = {Circulation},
  title        = {Identification of a Danger-Associated Peptide From Apolipoprotein B100 (ApoBDS-1) That Triggers Innate Proatherogenic Responses},
  url          = {http://dx.doi.org/10.1161/CIRCULATIONAHA.111.051599},
  volume       = {124},
  year         = {2011},
}