title: Effect of Simvastatin on 5-HT and 5-HTT in a Rat Model of Pulmonary Artery Hypertension.
abstract: OBJECTIVE
  To investigaterole of serotonin (5-HT) and serotonin transporter (5-HTT) in a rat model of cigarette smoke-induced pulmonary artery hypertension (PAH) and the effect of statins on regulating 5HT and 5-HTT.
  
  
  METHODS
  A rat model of COPD comorbid with PAH was established by cigarette smoke exposure with or without simvastatin administration. The smoking and the simvastatin plus smoking groups were exposed to cigarette smoke daily, and the latter received simvastatin at 5mg/kg, once a day. After 16 weeks of cigarette smoke exposure, body weight and mean pulmonary arterial pressure (mPAP) were measured, bronchoalveolar lavage (BAL) was performed, and lung tissues and blood samples were collected to determine cardiopulmonary pathology, physiological indices, blood levelof 5-HT and expression of 5-HTT in the lung.
  
  
  RESULTS
  In addition to alveolar structural damage (COPD-like injury), chronic cigarette smoke exposure lead to pulmonary artery remodeling and PAH as evidenced by significant elevation of mPAP, RVHI, WT%and WA%. Cigarette smoke exposure resulted in significant reduction in animal body weight, and simvastatin significantly prevented smoke-induced weight loss. The number of inflammatory cells in BALF was dramatically increased in smoke exposed rats, and simvastatin dampened the number of leukocytes, neutrophils, lymphocytes, and macrophages. In addition, circulating 5-HTand expression of 5-HTT in the lung were significantly increased in the smoked rats compared to control rats, and it was significantly reduced by simvastatin. Alteration of BALF inflammatory cells, 5-HT and 5-HTT was significantly correlated with changes of mPAP, RVHI, WT% and WA%.
  
  
  CONCLUSIONS
  Cigarette smoke exposure could result in not only COPD, but also PAH, which may attribute to the alteration of blood 5-HT and lung tissue 5-HTT. Simvastatin could significantly inhibited 5-HT and 5-HTT expression, and by which mechanism, it may protect animals from development of PAH.
authors.forename: Xue
authors.initials: X
authors.lastname: Jiang
authors.forename: LinDong
authors.initials: L
authors.lastname: Yuan
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.forename: Pengyu
authors.initials: P
authors.lastname: Wang
authors.forename: Lihai
authors.initials: L
authors.lastname: Zhang
authors.forename: Bojian
authors.initials: B
authors.lastname: Sun
authors.forename: Wuzhuang
authors.initials: W
authors.lastname: Sun
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000097:blood; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D012907:Smoking
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D019821:Simvastatin