title: Curcumin attenuates cardiac fibrosis in spontaneously hypertensive rats through PPAR-γ activation.
abstract: OBJECTIVE
  To investigate the effects of curcumin (Cur) on cardiac fibrosis in spontaneously hypertensive rats (SHRs) and the mechanisms underlying the anti-fibrotic effect of Cur in rat cardiac fibroblasts (CFs) in vitro.
  
  
  METHODS
  SHRs were orally treated with Cur (100 mg·kg(-1)·d(-1)) or Cur (100 mg·kg(-1)·d(-1)) plus the PPAR-γ antagonist GW9662 (1 mg·kg(-1)·d(-1)) for 12 weeks. Cultured CFs were treated with angiotensin II (Ang II, 0.1 μmol/L) in vitro. The expression of relevant proteins and mRNAs was analyzed using Western blotting and real-time PCR, respectively. The expression and activity of peroxisome proliferator-activated receptor-γ (PPAR-γ) were detected using Western blotting and a DNA-binding assay, respectively.
  
  
  RESULTS
  Treatment of SHRs with Cur significantly decreased systolic blood pressure, blood Ang II concentration, heart weight/body weight ratio and left ventricle weight/body weight ratio, with concurrently decreased expression of connective tissue growth factor (CTGF), plasminogen activator inhibitor (PAI)-1, collagen III (Col III) and fibronectin (FN), and increased expression and activity of PPAR-γ in the left ventricle. Co-treatment with GW9662 partially abrogated the anti-fibrotic effects of Cur in SHRs. Pretreatment of CFs with Cur (5, 10, 20 μmol/L) dose-dependently inhibited Ang II-induced expression of CTGF, PAI-1, Col III and FN, and increased the expression and binding activity of PPAR-γ. Pretreatment with GW9662 partially reversed anti-fibrotic effects of Cur in vitro. Furthermore, pretreatment of CFs with Cur inhibited Ang II-induced expression of transforming growth factor-β1 (TGF-β1) and phosphorylation of Smad2/3, which were reversed by GW9662.
  
  
  CONCLUSIONS
  Cur attenuates cardiac fibrosis in SHRs and inhibits Ang II-induced production of CTGF, PAI-1 and ECM in CFs in vitro. The crosstalk between PPAR-γ and TGF-β1/Smad2/3 signaling is involved in the anti-fibrotic and anti-proliferative effects of Cur.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Department of Thoracic Surgery, Taicang Affiliated Hospital of Soochow University, Taicang 215400, China.
authors.forename: Xin-hui
authors.initials: XH
authors.lastname: Yu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Taicang Affiliated Hospital of Soochow University, Taicang 215400, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024061:Collagen Type III / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy* / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects*; D008297:Male; D047495:PPAR gamma / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D024061:Collagen Type III; D005353:Fibronectins; D047495:PPAR gamma; D017395:Plasminogen Activator Inhibitor 1; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor; D003474:Curcumin