Montelukast inhibits matrix metalloproteinases expression in atherosclerotic rabbits.
BACKGROUND
Matrix metalloproteinases (MMPs) play important roles in the development and destabilization of atherosclerotic plaques. It is known that montelukast inhibits neointimal hyperplasia. However, the underlying mechanisms for the inhibitory effects of montelukast on neointimal formation have been poorly defined.


METHODS
Thirty-six male New Zealand White rabbits were randomized as normal control, placebo (0.9% NaCl, 1.5 ml/kg/day, via intraperitoneal injection), atorvastatin (atorvastatin, 1.5 mg/kg/day, orally) and montelukast groups (montelukast, 1.5 mg/kg/day, via intraperitoneal injection). Atherosclerosis was induced by balloon-injury and high-cholesterol (HC) diet. Serum lipids were measured at 0, 8 and 12 weeks. After 12 weeks, the rabbits were sacrificed and histopathological changes examined. Immunohistochemistry and reverse transcription-polymerase chain reaction were used to measure the expression of MMP-2 and MMP-9 in the plaques.


RESULTS
It was found that montelukast reduced neointimal formation, decreased macrophage accumulation, and increased smooth muscle cells. It also attenuated the expression of MMP-2 and MMP-9 in atherosclerotic plaques, but it had no effect on plasma lipid levels.


CONCLUSIONS
These data indicate that montelukast inhibits neointimal hyperplasia in association with decreased expression of MMP-2 and MMP-9 independent of plasma lipid levels in atherosclerotic plaques after vascular injury in hyperlipidemic rabbits.
Liu
Dezhi
D
Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, 305# East Zhongshan Road, Nanjing, 210002, Jiangsu Province, People's Republic of China.
Ge
Song
S
Zhou
Guangyi
G
Xu
Gelin
G
Zhang
Renliang
R
Zhu
Wusheng
W
Liu
Zhenguo
Z
Cheng
Songming
S
Liu
Xinfeng
X
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000069059:Atorvastatin; D003521:Cyclopropanes; D006538:Heptanoic Acids / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008264:Macrophages / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D011817:Rabbits; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013440:Sulfides
D000085:Acetates; D003521:Cyclopropanes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020024:Leukotriene Antagonists; D008055:Lipids; D011758:Pyrroles; D011804:Quinolines; D013440:Sulfides; D000069059:Atorvastatin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C093875:montelukast