Jin Ma1, Shi-Yu Ma2, Chun-Hua Ding3,4. 1. Cardiac Electrophysiology Research Lab, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510006, China. 2. Department of Critical Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510006, China. 3. Cardiac Electrophysiology Research Lab, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510006, China. dingmd@gmail.com. 4. Arrhythmia Center, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510006, China. dingmd@gmail.com.
Abstract
OBJECTIVE: To study the effect of curcumin on fibroblasts in rats with cardiac fibrosis. METHODS: The rats were randomly divided into 4 groups (n=12 in each group): the normal control, isoproterenol (ISO), ISO combined with low-dose curcumin (ISO+Cur-L), and ISO combined with high-dose curcumin (ISO+Cur-H) groups. ISO+Cur-L and ISO+Cur-H groups were treated with curcumin (150 or 300 mg•kg-1•day-1) for 28 days. The primary culture of rat cardiac fibroblast was processed by trypsin digestion method in vitro. The 3rd to 5th generation were used for experiment. Western blot method was used to test the expression of collagen type I/III, α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-β1, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to test the proliferation of fibroblast. RESULT: Curcumin significantly decreased interstitial and perivascular myocardial collagen deposition and cardiac weight index with reducing protein expression of collagen type I/III in hearts (P<0.05). In addition, curcumin directly inhibited angiotensin (Ang) II-induced fibroblast proliferation and collagen type I/III expression in cardiac fibroblasts (P<0.05). Curcumin also inhibited fibrosis by inhibiting myofibroblast differentiation, decreased TGF-β1, MMP-9 and TIMP-1 expression (P<0.05) but had no effects on Smad3 in Ang II incubated cardiac fibroblasts. CONCLUSIONS: Curcumin reduces cardiac fibrosis in rats and Ang II-induced fibroblast proliferation by inhibiting myofibroblast differentiation, decreasing collagen synthesis and accelerating collagen degradation through reduction of TGF-β1, MMPs/TIMPs. The present findings also provided novel insights into the role of curcumin as an antifibrotic agent for the treatment of cardiac fibrosis.
OBJECTIVE: To study the effect of curcumin on fibroblasts in rats with cardiac fibrosis. METHODS: The rats were randomly divided into 4 groups (n=12 in each group): the normal control, isoproterenol (ISO), ISO combined with low-dose curcumin (ISO+Cur-L), and ISO combined with high-dose curcumin (ISO+Cur-H) groups. ISO+Cur-L and ISO+Cur-H groups were treated with curcumin (150 or 300 mg•kg-1•day-1) for 28 days. The primary culture of rat cardiac fibroblast was processed by trypsin digestion method in vitro. The 3rd to 5th generation were used for experiment. Western blot method was used to test the expression of collagen type I/III, α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-β1, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to test the proliferation of fibroblast. RESULT: Curcumin significantly decreased interstitial and perivascular myocardial collagen deposition and cardiac weight index with reducing protein expression of collagen type I/III in hearts (P<0.05). In addition, curcumin directly inhibited angiotensin (Ang) II-induced fibroblast proliferation and collagen type I/III expression in cardiac fibroblasts (P<0.05). Curcumin also inhibited fibrosis by inhibiting myofibroblast differentiation, decreased TGF-β1, MMP-9 and TIMP-1 expression (P<0.05) but had no effects on Smad3 in Ang II incubated cardiac fibroblasts. CONCLUSIONS:Curcumin reduces cardiac fibrosis in rats and Ang II-induced fibroblast proliferation by inhibiting myofibroblast differentiation, decreasing collagen synthesis and accelerating collagen degradation through reduction of TGF-β1, MMPs/TIMPs. The present findings also provided novel insights into the role of curcumin as an antifibrotic agent for the treatment of cardiac fibrosis.
Authors: Xiaoping Yang; D Paul Thomas; Xiaochun Zhang; Bruce W Culver; Brenda M Alexander; William J Murdoch; Mysore N A Rao; David A Tulis; Jun Ren; Nair Sreejayan Journal: Arterioscler Thromb Vasc Biol Date: 2005-10-20 Impact factor: 8.311
Authors: James S Swaney; David M Roth; Erik R Olson; Jennifer E Naugle; J Gary Meszaros; Paul A Insel Journal: Proc Natl Acad Sci U S A Date: 2004-12-29 Impact factor: 11.205