title: Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model.
abstract: OBJECTIVE
  The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension (PAH). In this study we examined whether salvianolic acid A (SAA) extracted from the traditional Chinese medicine 'Dan Shen' attenuated vascular remodeling in a PAH rat model, and elucidated the underlying mechanisms.
  
  
  METHODS
  PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg/kg, sc). The rats were orally treated with either SAA (0.3, 1, 3 mg·kg(-1)·d(-1)) or a positive control bosentan (30 mg·kg(-1)·d(-1)) for 4 weeks. Echocardiography and hemodynamic measurements were performed on d 28. Then the hearts and lungs were harvested, the organ indices and pulmonary artery wall thickness were calculated, and biochemical and histochemical analysis were conducted. The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting.
  
  
  RESULTS
  Treatment with SAA or bosentan effectively ameliorated MCT-induced pulmonary artery remodeling, pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium, parenchymal injury and collagen deposition in the lungs. Moreover, the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs. The treatments partially restored MCT-induced reductions of bone morphogenetic protein type II receptor (BMPRII) and phosphorylated Smad1/5 in the lungs.
  
  
  CONCLUSIONS
  SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis. Thus, SAA may have therapeutic potential for the patients at high risk of PAH.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing 100050, China.
authors.forename: Yu-Cai
authors.initials: YC
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing 100050, China.
authors.forename: Tian-Yi
authors.initials: TY
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing 100050, China.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing 100050, China.
authors.forename: Dan-Shu
authors.initials: DS
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing 100050, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing 100050, China.
authors.forename: Zi-Ran
authors.initials: ZR
authors.lastname: Niu
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing 100050, China.
authors.forename: Yi-Huang
authors.initials: YH
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing 100050, China.
authors.forename: Lian-Hua
authors.initials: LH
authors.lastname: Fang
authors.affiliation: Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Guan-Hua
authors.initials: GH
authors.lastname: Du
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002109:Caffeic Acids / Q000737:chemistry / Q000627:therapeutic use*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D007773:Lactates / Q000737:chemistry / Q000627:therapeutic use*; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008297:Male; D016686:Monocrotaline; D009206:Myocardium / Q000473:pathology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza / Q000737:chemistry; D066253:Vascular Remodeling / Q000187:drug effects*
chemical_list: D002109:Caffeic Acids; D004365:Drugs, Chinese Herbal; D007773:Lactates; C066201:salvianolic acid A; D016686:Monocrotaline