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Blood, 15 July 2004, Vol. 104, No. 2, pp. 380-389. Prepublished online as a Blood First Edition Paper on March 30, 2004; DOI 10.1182/blood-2003-08-2961. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-08-2961v1 104/2/380    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Coleman, L. G. Articles by Gear, A. R. L. Search for Related Content PubMed PubMed Citation Articles by Coleman, L. G., Jr Articles by Gear, A. R. L. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY LDL oxidized by hypochlorous acid causes irreversible platelet aggregation when combined with low levels of ADP, thrombin, epinephrine, or macrophage-derived chemokine (CCL22) Leon G. Coleman, Jr, Renata K. Polanowska-Grabowska, Marek Marcinkiewicz, and Adrian R. L. Gear From the Department of Biochemistry and Molecular Genetics, University of Virginia Health Sciences Center, Charlottesville. The in vitro oxidation of low-density lipoprotein (LDL) by hypochlorous acid produces a modified form (HOCl-LDL) capable of stimulating platelet function. We now report that HOCl-LDL is highly effective at inducing platelet function, causing stable aggregation and -granule secretion. Such stimulation depended on the presence of low levels of primary agonists such as adenosine diphosphate (ADP) and thrombin, or others like epinephrine (EPI) and macrophage-derived chemokine (MDC, CCL22). Agonist levels, which by themselves induced little or reversible aggregation, caused strong stable aggregation when combined with low levels of HOCl-LDL. Platelet activation by HOCl-LDL and ADP (1 µM) caused P-selectin (CD62P) exposure, without serotonin or adenosine triphosphate (ATP) secretion. Intracellular calcium levels rose slowly (from 100 to 200 nM) in response to HOCl-LDL alone and rapidly when combined with ADP to about 300 nM. p38 mitogen-activated protein kinase (MAPK) became phosphorylated in response to HOCl-LDL alone. This phosphorylation was not blocked by the protein kinase C (PKC) inhibitor bisindolylmaleimide, which reduced the extent of aggregation and calcium increase. However, the p38 MAPK inhibitor SB203580 blocked platelet aggregation and phosphorylation of p38 MAPK. These findings suggest that HOCl-LDL exposed during atherosclerotic plaque rupture, coupled with low levels of primary agonists, can rapidly induce extensive and stable thrombus formation. (Blood. 2004;104:380-389) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Chen, M. Febbraio, W. Li, and R. L. Silverstein A Specific CD36-Dependent Signaling Pathway Is Required for Platelet Activation by Oxidized Low-Density Lipoprotein Circ. Res., June 20, 2008; 102(12): 1512 - 1519. [Abstract] [Full Text] [PDF] J. Rao, A. DiGiandomenico, J. Unger, Y. Bao, R. K. Polanowska-Grabowska, and J. B. Goldberg A novel oxidized low-density lipoprotein-binding protein from Pseudomonas aeruginosa Microbiology, February 1, 2008; 154(2): 654 - 665. [Abstract] [Full Text] [PDF] C. A. Gleissner, N. Leitinger, and K. Ley Effects of Native and Modified Low-Density Lipoproteins on Monocyte Recruitment in Atherosclerosis Hypertension, August 1, 2007; 50(2): 276 - 283. [Full Text] [PDF] C. V. Denis and D. D. Wagner Platelet Adhesion Receptors and Their Ligands in Mouse Models of Thrombosis Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 728 - 739. [Abstract] [Full Text] [PDF] B. S. Coller Leukocytosis and Ischemic Vascular Disease Morbidity and Mortality: Is It Time to Intervene? Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): 658 - 670. [Abstract] [Full Text] [PDF] S. J.A. Korporaal, G. Gorter, H. J.M. van Rijn, and J.-W. N. Akkerman Effect of Oxidation on the Platelet-Activating Properties of Low-Density Lipoprotein Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): 867 - 872. [Abstract] [Full Text] [PDF]

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