title: Fluoxetine inhibited extracellular matrix of pulmonary artery and inflammation of lungs in monocrotaline-treated rats.
abstract: OBJECTIVE
  To investigate the effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine on extracellular matrix (ECM) remodeling of the pulmonary artery and inflammation of the lungs in pulmonary arterial hypertension (PAH) induced by monocrotaline in rats.
  
  
  METHODS
  MCT-induced chronic PAH was established in Wistar rats. After treatment with fluoxetine for 3 weeks, pulmonary hemodynamic measurement and morphological investigation of lung tissues were undertaken. The main components of the ECM, elastin and collagen, were detected using Van Gieson stain and Orcein stain, respectively, or using Victoria-ponceau's double stain. The ECM proteolytic enzymes matrix metalloproteinase (MMP)-2 and MMP-9, and the tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2, were detected by Western blot. Inflammation of lung tissue was assayed using lung morphology and inflammatory cytokine expression.
  
  
  RESULTS
  Fluoxetine (2 and 10 mg/kg) significantly inhibited MCT-induced PAH, attenuated pulmonary arterial muscularization and ECM remodeling, and decreased MMP/TIMP expression. Fluoxetine also suppressed inflammatory responses in lung tissue and inhibited the expression of the inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), monocyte chemotactic protein (MCP-1) and intercellular adhesion molecule-1 (ICAM-1).
  
  
  CONCLUSIONS
  Fluoxetine inhibited MCT-induced ECM remodeling of the pulmonary artery and inflammation of lung tissue. These effects were related to its inhibition on MMPs/TIMPs and cytokine productions.
authors.affiliation: Department of Clinical Pharmacology, College of Pharmacy, China Medical University, Shenyang, China.
authors.forename: Xue-qin
authors.initials: XQ
authors.lastname: Li
authors.forename: Han-ming
authors.initials: HM
authors.lastname: Wang
authors.forename: Chun-guang
authors.initials: CG
authors.lastname: Yang
authors.forename: Xin-hua
authors.initials: XH
authors.lastname: Zhang
authors.forename: Dan-dan
authors.initials: DD
authors.lastname: Han
authors.forename: Huai-liang
authors.initials: HL
authors.lastname: Wang
mesh_terms: D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D065627:Familial Primary Pulmonary Hypertension; D005473:Fluoxetine / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D016686:Monocrotaline; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000037:antagonists & inhibitors
chemical_list: D016207:Cytokines; D005473:Fluoxetine; D061965:Matrix Metalloproteinase Inhibitors; D016686:Monocrotaline; D017367:Selective Serotonin Reuptake Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases