Zhe Meng1, Xin-hui Yu2, Jun Chen1, Ling Li1, Sheng Li2. 1. Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. 2. Department of Thoracic Surgery, Taicang Affiliated Hospital of Soochow University, Taicang 215400, China.
Abstract
AIM: 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. CONCLUSION: 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.
AIM: To investigate the effects of curcumin (Cur) on cardiac fibrosis in spontaneously hypertensiverats (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. CONCLUSION: 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: Karina Reyes-Gordillo; José Segovia; Mineko Shibayama; Victor Tsutsumi; Paula Vergara; Mario G Moreno; Pablo Muriel Journal: Fundam Clin Pharmacol Date: 2008-08 Impact factor: 2.748
Authors: Tao Zhu; Chanmei Shi; He Li; Jing He; Yanli Yang; Qin Wang; Xinyu Deng; Yanqiao Wu; Jing Wang; Yan Zhao; Huojin Deng Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2018-09-30