open access

Vol 76, No 8 (2018)
Original articles
Published online: 2018-05-25
Submitted: 2018-03-29
Accepted: 2018-05-23
Get Citation

Green tea polyphenol epigallocatechin-3-gallate increases atherosclerotic plaque stability in apolipoprotein E-deficient mice fed a high-fat diet

Qiming Wang, Jian Zhang, Yafei Li, Haojie Shi, Hao Wang, Bingrui Chen, Fang Wang, Zemu Wang, Zhijian Yang, Liansheng Wang
DOI: 10.5603/KP.a2018.0114
·
Pubmed: 29862488
·
Kardiol Pol 2018;76(8):1263-1270.

open access

Vol 76, No 8 (2018)
Original articles
Published online: 2018-05-25
Submitted: 2018-03-29
Accepted: 2018-05-23

Abstract

Background: Epigallocatechin-3-gallate (EGCG), which is the principal component of green tea, has been shown to prevent atherosclerosis. However, the effect of EGCG on atherosclerotic plaque stability remains unknown.

Aim: This study aimed to assess whether EGCG can enhance atherosclerotic plaque stability and to investigate the underlying mechanisms.

Methods: Apolipoprotein E-deficient mice fed a high-fat diet were injected intraperitoneally with EGCG (10 mg/kg) for 16 weeks. Cross sections of the brachiocephalic arteries were stained with haematoxylin and eosin for morphometric analyses or Masson’s trichrome for collagen content analyses. Immunohistochemistry was performed to evaluate the percentage of macrophages and smooth muscle cells (SMCs). Protein expression and matrix metalloproteinase (MMP) activity were assayed by Western blot and gelatin zymography, respectively. Serum inflammatory cytokine levels were quantified by enzyme-linked immunosorbent assays.

Results: After 16 weeks of feeding the high-fat diet, there were clear atherosclerotic lesions in the proximal brachiocephalic artery segments according to HE staining. EGCG treatment significantly increased the thickness of the fibrous cap. In the atherosclerotic plaques of the EGCG group, the relative macrophage content was decreased, whereas the relative SMC and collagen contents were increased. The expression levels of MMP-2, MMP-9, and extracellular matrix metalloproteinase inducer (EMMPRIN) were significantly decreased by EGCG treatment. In addition, EGCG treatment decreased the circulat­ing tumour necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, and interferon-γ levels in apolipoprotein E-deficient mice.

Conclusions: EGCG promotes atherosclerotic lesion stability in apolipoprotein E-deficient mice. Potentially, these effects are mediated through the inhibition of inflammatory cytokine, MMPs and EMMPRIN expression.

Abstract

Background: Epigallocatechin-3-gallate (EGCG), which is the principal component of green tea, has been shown to prevent atherosclerosis. However, the effect of EGCG on atherosclerotic plaque stability remains unknown.

Aim: This study aimed to assess whether EGCG can enhance atherosclerotic plaque stability and to investigate the underlying mechanisms.

Methods: Apolipoprotein E-deficient mice fed a high-fat diet were injected intraperitoneally with EGCG (10 mg/kg) for 16 weeks. Cross sections of the brachiocephalic arteries were stained with haematoxylin and eosin for morphometric analyses or Masson’s trichrome for collagen content analyses. Immunohistochemistry was performed to evaluate the percentage of macrophages and smooth muscle cells (SMCs). Protein expression and matrix metalloproteinase (MMP) activity were assayed by Western blot and gelatin zymography, respectively. Serum inflammatory cytokine levels were quantified by enzyme-linked immunosorbent assays.

Results: After 16 weeks of feeding the high-fat diet, there were clear atherosclerotic lesions in the proximal brachiocephalic artery segments according to HE staining. EGCG treatment significantly increased the thickness of the fibrous cap. In the atherosclerotic plaques of the EGCG group, the relative macrophage content was decreased, whereas the relative SMC and collagen contents were increased. The expression levels of MMP-2, MMP-9, and extracellular matrix metalloproteinase inducer (EMMPRIN) were significantly decreased by EGCG treatment. In addition, EGCG treatment decreased the circulat­ing tumour necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1, and interferon-γ levels in apolipoprotein E-deficient mice.

Conclusions: EGCG promotes atherosclerotic lesion stability in apolipoprotein E-deficient mice. Potentially, these effects are mediated through the inhibition of inflammatory cytokine, MMPs and EMMPRIN expression.

Get Citation

Keywords

epigallocatechin-3-gallate, atherosclerosis, plaque stability, inflammatory responses, matrix metalloproteinases

About this article
Title

Green tea polyphenol epigallocatechin-3-gallate increases atherosclerotic plaque stability in apolipoprotein E-deficient mice fed a high-fat diet

Journal

Kardiologia Polska (Polish Heart Journal)

Issue

Vol 76, No 8 (2018)

Pages

1263-1270

Published online

2018-05-25

DOI

10.5603/KP.a2018.0114

Pubmed

29862488

Bibliographic record

Kardiol Pol 2018;76(8):1263-1270.

Keywords

epigallocatechin-3-gallate
atherosclerosis
plaque stability
inflammatory responses
matrix metalloproteinases

Authors

Qiming Wang
Jian Zhang
Yafei Li
Haojie Shi
Hao Wang
Bingrui Chen
Fang Wang
Zemu Wang
Zhijian Yang
Liansheng Wang

References (27)
  1. Finn AV, Nakano M, Narula J, et al. Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol. 2010; 30(7): 1282–1292.
  2. Newby AC. Metalloproteinase expression in monocytes and macrophages and its relationship to atherosclerotic plaque instability. Arterioscler Thromb Vasc Biol. 2008; 28(12): 2108–2114.
  3. Libby P, Aikawa M. Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat Med. 2002; 8(11): 1257–1262.
  4. Zhang YF, Xu Q, Lu J, et al. Tea consumption and the incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Eur J Cancer Prev. 2015; 24(4): 353–362.
  5. Kokubo Y, Iso H, Saito I, et al. The impact of green tea and coffee consumption on the reduced risk of stroke incidence in Japanese population: the Japan public health center-based study cohort. Stroke. 2013; 44(5): 1369–1374.
  6. Babu PV, Liu D. Green tea catechins and cardiovascular health: an update. Curr Med Chem. 2008; 15(18): 1840–1850.
  7. Legeay S, Rodier M, Fillon L, et al. Epigallocatechin gallate: a review of its beneficial properties to prevent metabolic syndrome. Nutrients. 2015; 7(7): 5443–5468.
  8. Oz H. Chronic inflammatory diseases and green tea polyphenols. Nutrients. 2017; 9(6): 561.
  9. Wang ZM, Gao W, Wang H, et al. Green tea polyphenol epigallocatechin-3-gallate inhibits TNF-α-induced production of monocyte chemoattractant protein-1 in human umbilical vein endothelial cells. Cell Physiol Biochem. 2014; 33(5): 1349–1358.
  10. Lagha AB, Grenier D. Tea polyphenols inhibit the activation of NF-κB and the secretion of cytokines and matrix metalloproteinases by macrophages stimulated with Fusobacterium nucleatum. Sci Rep. 2016; 6: 34520.
  11. Lee MiH, Kwon BJ, Koo MA, et al. Mitogenesis of vascular smooth muscle cell stimulated by platelet-derived growth factor-bb is inhibited by blocking of intracellular signaling by epigallocatechin-3-O-gallate. Oxid Med Cell Longev. 2013; 2013: 827905.
  12. Wang QM, Wang H, Li YF, et al. Inhibition of EMMPRIN and MMP-9 Expression by Epigallocatechin-3-Gallate through 67-kDa Laminin Receptor in PMA-Induced Macrophages. Cell Physiol Biochem. 2016; 39(6): 2308–2319.
  13. Chyu KY, Babbidge SM, Zhao X, et al. Differential effects of green tea-derived catechin on developing versus established atherosclerosis in apolipoprotein E-null mice. Circulation. 2004; 109(20): 2448–2453.
  14. Liu H, Yang Lx, Guo Rw, et al. Functional blockage of EMMPRIN ameliorates atherosclerosis in apolipoprotein E-deficient mice. Int J Cardiol. 2013; 168(4): 3248–3253.
  15. Schmidt R, Bültmann A, Ungerer M, et al. Extracellular matrix metalloproteinase inducer regulates matrix metalloproteinase activity in cardiovascular cells: implications in acute myocardial infarction. Circulation. 2006; 113(6): 834–841.
  16. Wang QM, Gong QY, Yan JJ, et al. Association between green tea intake and coronary artery disease in a Chinese population. Circ J. 2010; 74(2): 294–300.
  17. Wang ZM, Zhou Bo, Wang YS, et al. Black and green tea consumption and the risk of coronary artery disease: a meta-analysis. Am J Clin Nutr. 2011; 93(3): 506–515.
  18. Pang J, Zhang Z, Zheng Tz, et al. Green tea consumption and risk of cardiovascular and ischemic related diseases: A meta-analysis. Int J Cardiol. 2016; 202: 967–974.
  19. Lee RT, Schoen FJ, Loree HM, et al. Circumferential stress and matrix metalloproteinase 1 in human coronary atherosclerosis. Implications for plaque rupture. Arterioscler Thromb Vasc Biol. 1996; 16(8): 1070–1073.
  20. Page-McCaw A, Ewald AJ, Werb Z. Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol. 2007; 8(3): 221–233.
  21. Kai H, Ikeda H, Yasukawa H, et al. Peripheral blood levels of matrix metalloproteases-2 and -9 are elevated in patients with acute coronary syndromes. J Am Coll Cardiol. 1998; 32(2): 368–372.
  22. Fiotti N, Altamura N, Orlando C, et al. Metalloproteinases-2, -9 and TIMP-1 expression in stable and unstable coronary plaques undergoing PCI. Int J Cardiol. 2008; 127(3): 350–357.
  23. Biswas C, Zhang Y, DeCastro R, et al. The human tumor cell-derived collagenase stimulatory factor (renamed EMMPRIN) is a member of the immunoglobulin superfamily. Cancer Res. 1995; 55(2): 434–439.
  24. Joghetaei N, Stein A, Byrne RA, et al. The Extracellular Matrix Metalloproteinase Inducer (EMMPRIN, CD147): a potential novel target in atherothrombosis prevention? Thromb Res. 2013; 131(6): 474–480.
  25. Uchiyama Y, Suzuki T, Mochizuki K, et al. Dietary supplementation with a low dose of (-)-epigallocatechin-3-gallate reduces pro-inflammatory responses in peripheral leukocytes of non-obese type 2 diabetic GK rats. J Nutr Sci Vitaminol (Tokyo). 2013; 59(6): 541–547.
  26. Wang W, Zhang ZZ, Wu Y, et al. (-)-Epigallocatechin-3-Gallate Ameliorates Atherosclerosis and Modulates Hepatic Lipid Metabolic Gene Expression in Apolipoprotein E Knockout Mice: Involvement of TTC39B. Front Pharmacol. 2018; 9: 195.
  27. Zhong W, Huan XD, Cao Q, et al. Cardioprotective effect of epigallocatechin-3-gallate against myocardial infarction in hypercholesterolemic rats. Exp Ther Med. 2015; 9(2): 405–410.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., Świętokrzyska 73 street, 80–180 Gdańsk, Poland

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: viamedica@viamedica.pl