Pterostilbene Inhibits Vascular Smooth Muscle Cells Migration and Matrix Metalloproteinase-2 through Modulation of MAPK Pathway

J Food Sci. 2015 Oct;80(10):H2331-5. doi: 10.1111/1750-3841.13002. Epub 2015 Sep 26.

Abstract

Smooth muscle cells (SMCs) migration and matrix metalloproteinase-2 (MMP-2) activation are main roles in atherosclerosis. Pterostilbene (trans-3, 5-dimethoxy-4-hydroxystilbene) is known to have various pharmacologic effects such as anti-inflammatory and anticarcinogenic properties. The present study aimed to investigate the anti-atheroscleroic property of pterostilbene in the rat smooth muscle cell (SMC) A7r9 cell lines and the underlying mechanisms. In this study, pterostilbene treatment significantly inhibited migration/invasion capacities of in A7r9 cell. Pterostilbene was also found to significantly decreased MMP-2 activity and expression by gelatin zymography and western blot assay in SMC. In the MAPK signaling pathway, western blot assay also indicated that pterostilbene up-regulated the phosphorylation of extracellular-signal-regulated kinase (Erk)1/2. Moreover, inhibition of Erk1/2 by specific inhibitors significantly abolished the pterostilbene-decreased expression of MMP-2 and migration/invasion capacities. These findings suggest that pterostilbene inhibited SMC migration and that MMP-2 activation could be mediated via Erk1/2 phosphorylation. It is further possible that pterostilbene could play a novel role in the treatment of atherosclerosis.

Practical application: Pterostilbene is a plant polyphenol compound that is principally found in blueberries. In this study, we found that pterostilbene could inhibit SMCs migration via down-regulation of MMP-2. Particularly, expression of MMP-2 was found to be strongly associated with the phosphorylation of Erk1/2.

Keywords: matrix metalloproteinase-2; migration; pterostilbene; smooth muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta
  • Atherosclerosis / metabolism
  • Blueberry Plants / chemistry*
  • Cell Movement / drug effects*
  • Down-Regulation
  • Male
  • Matrix Metalloproteinase 2 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Phosphorylation
  • Plant Extracts / pharmacology*
  • Rats
  • Signal Transduction
  • Stilbenes / pharmacology*
  • Up-Regulation

Substances

  • Plant Extracts
  • Stilbenes
  • pterostilbene
  • 4-hydroxystilbene
  • Mitogen-Activated Protein Kinase 3
  • Matrix Metalloproteinase 2