Prominent Lectin-Like Oxidized Low Density Lipoprotein (LDL) Receptor-1 (LOX-1) Expression in Atherosclerotic Lesions Is Associated with Tissue Factor Expression and Apoptosis in Hypercholesterolemic Rabbits

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Author(s)

    • Kuge Yuji KUGE Yuji
    • Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University
    • TAKAI Nozomi
    • Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University
    • OGAWA Yuki
    • Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University
    • MUKAI Takahiro
    • Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University
    • MINAMI Manabu
    • Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University
    • SHIOMI Masashi
    • Institute for Experimental Animals, Kobe University School of Medicine
    • SAJI Hideo
    • Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University

Abstract

Background: Despite increasing <i>in vitro</i> evidence that lectin-like oxidized low density lipoprotein (LDL) receptor-1 (LOX-1), a cell-surface receptor for oxidized LDL, is implicated in the atherogenesis and thrombus formation, its <i>in vivo</i> participation to the atherosclerotic plaque destabilization, rupture and thrombus formation remains unclear. Here, we compared the <i>in vivo</i> expression of LOX-1, with tissue factor (TF) expression and cell apoptosis, in atherosclerotic lesions of myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits. Methods and Results: We prepared sixty series of cross sections in the aortic arch and the thoracic aorta from four WHHLMI rabbits. LOX-1 and TF expression, as well as apoptotic events were determined by immunohistochemical staining and TUNEL methods, respectively. LOX-1 expression was mainly observed in the macrophage-rich lipid areas of vulnerable plaque-like atheromatous lesions where TF expression and apoptotic events were prominent. LOX-1 expression was positively correlated with TF expression (<i>r</i>=0.53, <i>p</i><0.0001), apoptotic events (<i>r</i>=0.52, <i>p</i><0.0001) and morphological vulnerability (<i>r</i>=0.63, <i>p</i><0.0001). Conclusions: LOX-1 expression appears to be closely associated with TF expression, apoptotic events and the morphological vulnerability, suggesting the <i>in vivo</i> involvement of LOX-1 in the destabilization and rupture of atherosclerotic lesions and the subsequent thrombus formation. The present findings in hypercholesterolemic rabbits should help advance our understanding of the pathophysiology of atherosclerosis.

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 31(8), 1475-1482, 2008-08-01

    Pharmaceutical Society of Japan

References:  35

Cited by:  3

Codes

  • NII Article ID (NAID)
    110006839004
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    09186158
  • NDL Article ID
    9587326
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-V41
  • Data Source
    CJP  CJPref  NDL  NII-ELS  IR  J-STAGE 
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