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

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

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Publication Article, peer reviewed scientific
Title Identification of a Danger-Associated Peptide From Apolipoprotein B100 (ApoBDS-1) That Triggers Innate Proatherogenic Responses
Author(s) Ketelhuth, Daniel ; Rios, FJO ; Wang, Y ; Liu, H ; Johansson, ME ; Nordin Fredrikson, Gunilla ; Hedin, Ulf ; Gidlund, Magnus ; Nilsson, Jan ; Hansson, Göran K ; Yan, Zhong-qun
Date 2011
English 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.
DOI http://dx.doi.org/10.1161/CIRCULATIONAHA.111.051599 (link to publisher's fulltext)
Publisher Lippincott Williams & Wilkins
Host/Issue Circulation;22
Volume 124
ISSN 1524-4539
Pages 2433-2443
Language eng (iso)
Subject(s) apolipoprotein B100
atherosclerosis
innate immunity
macrophage
oxidized LDL
Medicine
Research Subject Categories::MEDICINE
Handle http://hdl.handle.net/2043/12844 (link to this page)

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