title: 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.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. kuge@med.hokudai.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kume
authors.forename: Seigo
authors.initials: S
authors.lastname: Ishino
authors.forename: Nozomi
authors.initials: N
authors.lastname: Takai
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mukai
authors.forename: Manabu
authors.initials: M
authors.lastname: Minami
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiomi
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D017209:Apoptosis / Q000502:physiology*; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006937:Hypercholesterolemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008264:Macrophages / Q000473:pathology; D011817:Rabbits; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D013925:Thromboplastin / Q000096:biosynthesis*
chemical_list: D011973:Receptors, LDL; D013925:Thromboplastin