Lectin-like oxidized LDL receptor-1 (LOX-1) expression is associated with atherosclerotic plaque instability--analysis in hypercholesterolemic rabbits.
Lectin-like oxidized LDL receptor-1 (LOX-1), a cell-surface receptor for oxidized LDL (Ox-LDL), has been implicated in vascular cell dysfunction related to atherosclerotic plaque instability, according to cell culture experiments. In the present study, we investigated the relationship between LOX-1 expression and plaque instability in hypercholesterolemic rabbits by immunohistological analyses in vivo. We prepared thirty series of cross sections of the thoracic aorta from six myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits (12-24 months), in which seventy atherosclerotic plaques were observed. LOX-1, matrix metalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1) expression, apoptotic events, plaque instability index (an index of the morphological destabilization of atherosclerotic plaques) and fibromuscular cap thickness in each atherosclerotic plaque were determined by immunohistochemical staining, TUNEL staining and Azan-Mallory staining. LOX-1 expression was positively correlated with the plaque instability index and MMP-9 expression. LOX-1 expression was more prominent in atherosclerotic plaques with thinner fibromuscular cap (<100 microm). Furthermore, LOX-1 expression was shown in the macrophage-rich lipid core area where MCP-1 expression and apoptotic events were prominent. These results indicate that enhanced LOX-1 expression was associated with histologically unstable atherosclerotic plaques in hypercholesterolemic rabbits, suggesting the involvement of LOX-1 in the destabilization of atherosclerotic plaques in vivo.
Ishino
Seigo
S
Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Mukai
Takahiro
T
Kume
Noriaki
N
Asano
Daigo
D
Ogawa
Mikako
M
Kuge
Yuji
Y
Minami
Manabu
M
Kita
Toru
T
Shiomi
Masashi
M
Saji
Hideo
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis; D050197:Atherosclerosis; D018932:Chemokine CCL2 / Q000096:biosynthesis; D005786:Gene Expression Regulation; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008954:Models, Biological; D011817:Rabbits; D051127:Scavenger Receptors, Class E / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D018932:Chemokine CCL2; C495667:MCP1 protein, rabbit; D051127:Scavenger Receptors, Class E; D020780:Matrix Metalloproteinase 9