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 circulat-ing 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.
Keywords: atherosclerosis; epigallocatechin-3-gallate; inflammatory responses; matrix metalloproteinases; plaque stability.