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Curcumin reduces cardiac fibrosis by inhibiting myofibroblast differentiation and decreasing transforming growth factor β1 and matrix metalloproteinase 9 / tissue inhibitor of metalloproteinase 1

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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.

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Authors and Affiliations

  1. Cardiac Electrophysiology Research Lab, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, 510006, China

    Jin Ma  (马 金) & Chun-hua Ding  (丁春华)

  2. Department of Critical Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510006, China

    Shi-yu Ma  (马世玉)

  3. Arrhythmia Center, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510006, China

    Chun-hua Ding  (丁春华)

Authors
  1. Jin Ma  (马 金)
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  2. Shi-yu Ma  (马世玉)
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  3. Chun-hua Ding  (丁春华)
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Corresponding author

Correspondence to Chun-hua Ding  (丁春华).

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Ma, J., Ma, Sy. & Ding, Ch. Curcumin reduces cardiac fibrosis by inhibiting myofibroblast differentiation and decreasing transforming growth factor β1 and matrix metalloproteinase 9 / tissue inhibitor of metalloproteinase 1. Chin. J. Integr. Med. 23, 362–369 (2017). https://doi.org/10.1007/s11655-015-2159-5

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  • DOI: https://doi.org/10.1007/s11655-015-2159-5

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