title: Triptolide protects rat heart against pressure overload-induced cardiac fibrosis.
abstract: BACKGROUND
  Emerging evidence underlines the role of inflammation activation in the process of cardiac fibrosis. Triptolide has potent anti-inflammatory and anti-proliferative properties, and extensively used in the treatment of chronic inflammatory disorders. In the current study, we test the hypothesis that triptolide treatment facilitates to attenuate chronic pressure overload-induced cardiac fibrosis in a model of rat.
  
  
  METHODS
  Adult male Sprague-Dawley rats were subjected to a suprarenal abdominal aorta constriction (AC) or sham (as control) to induce sustained pressure overload. Eight weeks later, rats were randomly assigned to receive triptolide (9 μg/kg.d, i.p) or vehicle (0.1% dimethyl sulfoxide, 0.2 ml/d, i.p) treatment for an additional 8 weeks.
  
  
  RESULTS
  AC caused significant pathological hypertrophy, cardiac fibrosis and reduced cardiac diastolic function. Triptolide treatment markedly inhibited AC-induced increases in myocardial collagen volume fraction, collagen type I/III deposition, left ventricular end-diastolic pressure, expressions of pro-fibrogenic factors (transforming growth factor-β and angiotensin II) and pro-inflammatory cytokines (IL-1β and IL-6), NF-κB activation and inflammatory cell infiltration in left ventricles compared with vehicle, without affecting cardiac hypertrophy. However, triptolide had no effects on systemic blood pressure and circulating angiotensin II level.
  
  
  CONCLUSIONS
  Collectively, the findings suggested that triptolide treatment elicits favorable anti-fibrogenic effect in a blood pressure-independent manner, at least in part, through inhibiting myocardial pro-fibrogenic factor production and inflammatory activation in the pressure overloaded heart.
authors.affiliation: Department of Cardiology, the Second Clinic Medical College, Yangzhou University, Yangzhou, 225001, China; Department of Clinical Medicine, Yangzhou University Medical College, Yangzhou, 225001, China.
authors.forename: Zhengang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xinkai
authors.initials: X
authors.lastname: Qu
authors.forename: Yue
authors.initials: Y
authors.lastname: Ni
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Dong
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Yan
authors.forename: Jianhua
authors.initials: J
authors.lastname: Qin
authors.forename: Hongguang
authors.initials: H
authors.lastname: Sun
authors.forename: Yongling
authors.initials: Y
authors.lastname: Ding
authors.forename: Pei
authors.initials: P
authors.lastname: Zhao
authors.forename: Kaizheng
authors.initials: K
authors.lastname: Gong
mesh_terms: D000818:Animals; D004224:Diterpenes / Q000627:therapeutic use*; D004852:Epoxy Compounds / Q000627:therapeutic use; D005355:Fibrosis / Q000209:etiology / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D009206:Myocardium / Q000473:pathology*; D010616:Phenanthrenes / Q000627:therapeutic use*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D010616:Phenanthrenes; C001899:triptolide
keywords: Angiotensin II; Cardiac fibrosis; Inflammation; NF-κB; Triptolide