Oxidized LDL receptor LOX-1 is involved in neointimal hyperplasia after balloon arterial injury in a rat model.
OBJECTIVE
LOX-1 is a multi-ligand receptor originally identified as the endothelial oxidized LDL receptor. LOX-1 expression is also induced in smooth muscle cells in response to proinflammatory and oxidative stimuli. Here, we report on the role of LOX-1 in intimal hyperplasia, in which proinflammatory and oxidative stimuli are increased.


RESULTS
Left common carotid artery of rat was injured by a balloon catheter. The expression of LOX-1 was significantly increased within 24 h after the balloon injury and peaked at day 7. LOX-1 expression was observed predominantly in medial smooth muscle cells until day 3, and then shifted to predominantly intimal smooth muscle cells. At day 14, the expression was concentrated in the regenerated endothelial cells. To examine the contributory role of LOX-1 in the growth of intimal smooth muscle cells, rats were administered anti-LOX1 antibody intravenously every 3 days after balloon injury. Anti-LOX-1 antibody administration effectively suppressed intimal hyperplasia, oxidative stress, and leukocyte infiltration compared with control IgG. These findings suggest the importance of LOX-1 expression in the pathogenesis of neointimal formation in conjunction with oxidative stress and leukocyte infiltration.


CONCLUSIONS
The LOX-1 expressed in smooth muscle cells is involved in intimal hyperplasia in a rat model of balloon injury. Manipulation of LOX-1 activity is a novel potential therapeutic target to prevent restenosis after angioplasty.
Hinagata
Jun-ichi
J
Department of Vascular Physiology, National Cardiovascular Center Research Institute, Suita, Osaka 565-8565, Japan.
Kakutani
Makoto
M
Fujii
Takao
T
Naruko
Takahiko
T
Inoue
Nobutaka
N
Fujita
Yoshiko
Y
Mehta
Jawahar L
JL
Ueda
Makiko
M
Sawamura
Tatsuya
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016466:CHO Cells; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology*; D017536:Carotid Artery, Common / Q000378:metabolism / Q000473:pathology*; D002404:Catheterization / Q000009:adverse effects; D006224:Cricetinae; D015870:Gene Expression; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008856:Microscopy, Fluorescence; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology*
D000911:Antibodies, Monoclonal; C495136:OLR1 protein, rat; D017382:Reactive Oxygen Species; D051127:Scavenger Receptors, Class E