title: Montelukast inhibits matrix metalloproteinases expression in atherosclerotic rabbits.
abstract: 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.
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, 305# East Zhongshan Road, Nanjing, 210002, Jiangsu Province, People's Republic of China.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Liu
authors.forename: Song
authors.initials: S
authors.lastname: Ge
authors.forename: Guangyi
authors.initials: G
authors.lastname: Zhou
authors.forename: Gelin
authors.initials: G
authors.lastname: Xu
authors.forename: Renliang
authors.initials: R
authors.lastname: Zhang
authors.forename: Wusheng
authors.initials: W
authors.lastname: Zhu
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Liu
authors.forename: Songming
authors.initials: S
authors.lastname: Cheng
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
mesh_terms: 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
chemical_list: 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