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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  • Kuge Yuji
    Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University Department of Tracer Kinetics & Bioanalysis, Graduate School of Medicine, Hokkaido University
  • Kume Noriaki
    Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University
  • Ishino Seigo
    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

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Background: Despite increasing in vitro 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 in vivo participation to the atherosclerotic plaque destabilization, rupture and thrombus formation remains unclear. Here, we compared the in vivo 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 (r=0.53, p<0.0001), apoptotic events (r=0.52, p<0.0001) and morphological vulnerability (r=0.63, p<0.0001). Conclusions: LOX-1 expression appears to be closely associated with TF expression, apoptotic events and the morphological vulnerability, suggesting the in vivo 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.

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