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    Human Neutrophil Peptides Mediate Endothelial-Monocyte Interaction, Foam Cell Formation, and Platelet Activation

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    Quinn_AHA_2011.pdf (1.178Mb)
    Issue Date
    2011-09
    Author
    Quinn, Kieran
    Henriques, Melanie
    Tabuchi, Arata
    Han, Bing
    Yang, Hong
    Cheng, Wei-Erh
    Tole, Soumitra
    Yu, Hanpo
    Luo, Alice
    Charbonney, Emmanuel
    Tullis, Elizabeth
    Lazarus, Alan
    Robinson, Lisa
    Ni, Heyu
    Peterson, Blake R.
    Kuebler, Wolfgang
    Slutsky, Arthur
    Zhang, Haibo
    Publisher
    American Heart Association
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    © 2011 American Heart Association, Inc
    Metadata
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    Abstract
    Objective—Neutrophils are involved in the inflammatory responses during atherosclerosis. Human neutrophil peptides (HNPs) released from activated neutrophils exert immune modulating properties. We hypothesized that HNPs play an important role in neutrophil-mediated inflammatory cardiovascular responses in atherosclerosis. Methods and Results—We examined the role of HNPs in endothelial-leukocyte interaction, platelet activation, and foam cell formation in vitro and in vivo. We demonstrated that stimulation of human coronary artery endothelial cells with clinically relevant concentrations of HNPs resulted in monocyte adhesion and transmigration; induction of oxidative stress in human macrophages, which accelerates foam cell formation; and activation and aggregation of human platelets. The administration of superoxide dismutase or anti-CD36 antibody reduced foam cell formation and cholesterol efflux. Mice deficient in double genes of low-density lipoprotein receptor and low-density lipoprotein receptor–related protein (LRP), and mice deficient in a single gene of LRP8, the only LRP phenotype expressed in platelets, showed reduced leukocyte rolling and decreased platelet aggregation and thrombus formation in response to HNP stimulation. Conclusion—HNPs exert proatherosclerotic properties that appear to be mediated through LRP8 signaling pathways, suggesting an important role for HNPs in the development of inflammatory cardiovascular diseases.
    URI
    http://hdl.handle.net/1808/24042
    DOI
    https://doi.org/10.1161/ATVBAHA.111.227116
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    • Medicinal Chemistry Scholarly Works [242]
    Citation
    Quinn, K. L., Henriques, M., Tabuchi, A., Han, B., Yang, H., Cheng, W.-E., … Zhang, H. (2011). Human Neutrophil Peptides Mediate Endothelial-Monocyte Interaction, Foam Cell Formation, and Platelet Activation. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(9), 2070–2079. http://doi.org/10.1161/ATVBAHA.111.227116

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    KU Libraries
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    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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