Cheng-Chih Chung1, Yu-Hsun Kao2, Jing-Ping Liou3, Yi-Jen Chen1. 1. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University; ; Division of Cardiovascular Medicine, Department of Internal Medicine; 2. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University; ; Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University; 3. School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Abstract
BACKGROUND: Cardiac fibrosis plays a critical role in the pathophysiology of cardiovascular disease. It has been observed that curcumin has several cardiovascular effects. The purpose of this study was to evaluate whether curcumin can attenuate cardiac fibroblasts activity. METHODS AND RESULTS: We evaluated the migration, proliferation, collagen production, and transcription signaling in rat cardiac fibroblasts isolated from Sprague-Dawley rats (males, weighing 300-350 g) that were or were not incubated with curcumin (25 μM) and the co-administration of transforming growth factor (TGF)- β1 (10 ng/ml) or angiotensin (Ang) II (100 nM) by a cell migration analysis, proliferation assay, and Western blot analysis. Compared to those without curcumin, curcumin-treated cardiac fibroblasts exhibited lower migratory, proliferative abilities and collagen production at the baseline and after the co-administration of TGF-β1 or Ang II. Curcumin-treated cardiac fibroblasts had increased matrix metalloproteinase (MMP)-2 activity in the presence of Ang II treatment. Curcumin-treated cardiac fibroblasts down-regulated phosphorylated protein kinase B (Akt) and phosphorylated Smad2/3 expression irrespective of TGF-β1 treatment. Curcumin also decreased phosphorylated extracellular signal-regulated kinase (ERK)1/2 levels in the presence of Ang II. CONCLUSIONS: Curcumin attenuated Akt, Smad2/3, and ERK1/2 phosphorylation which were mediated by TGF-β1 and angiotensin II. This resulted in decreased cardiac fibroblast activation and supports the assertion that curcumin is an effective antifibrotic agent which can be used to treat heart failure. KEY WORDS: Angiotensin; Curcumin; Fibroblasts; Heart failure; Transforming growth factor.
BACKGROUND: Cardiac fibrosis plays a critical role in the pathophysiology of cardiovascular disease. It has been observed that curcumin has several cardiovascular effects. The purpose of this study was to evaluate whether curcumin can attenuate cardiac fibroblasts activity. METHODS AND RESULTS: We evaluated the migration, proliferation, collagen production, and transcription signaling in rat cardiac fibroblasts isolated from Sprague-Dawley rats (males, weighing 300-350 g) that were or were not incubated with curcumin (25 μM) and the co-administration of transforming growth factor (TGF)- β1 (10 ng/ml) or angiotensin (Ang) II (100 nM) by a cell migration analysis, proliferation assay, and Western blot analysis. Compared to those without curcumin, curcumin-treated cardiac fibroblasts exhibited lower migratory, proliferative abilities and collagen production at the baseline and after the co-administration of TGF-β1 or Ang II. Curcumin-treated cardiac fibroblasts had increased matrix metalloproteinase (MMP)-2 activity in the presence of Ang II treatment. Curcumin-treated cardiac fibroblasts down-regulated phosphorylated protein kinase B (Akt) and phosphorylated Smad2/3 expression irrespective of TGF-β1 treatment. Curcumin also decreased phosphorylated extracellular signal-regulated kinase (ERK)1/2 levels in the presence of Ang II. CONCLUSIONS:Curcumin attenuated Akt, Smad2/3, and ERK1/2 phosphorylation which were mediated by TGF-β1 and angiotensin II. This resulted in decreased cardiac fibroblast activation and supports the assertion that curcumin is an effective antifibrotic agent which can be used to treat heart failure. KEY WORDS: Angiotensin; Curcumin; Fibroblasts; Heart failure; Transforming growth factor.
Authors: A Ramirez Boscá; A Soler; M A Carrión-Gutiérrez; D Pamies Mira; J Pardo Zapata; J Diaz-Alperi; A Bernd; E Quintanilla Almagro; J Miquel Journal: Mech Ageing Dev Date: 2000-04-14 Impact factor: 5.432
Authors: Christina E Squires; G Patricia Escobar; John F Payne; Robert A Leonardi; Danielle K Goshorn; Nina J Sheats; I Matthew Mains; Joseph T Mingoia; English C Flack; Merry L Lindsey Journal: J Mol Cell Cardiol Date: 2005-10 Impact factor: 5.000