Dexamethasone inhibits vascular smooth muscle cell migration via modulation of matrix metalloproteinase activity

C. Pross, M. M. Farooq, N. Angle, J. S. Lane, J. J. Cerveira, A. E. Xavier, J. A. Freischlag, R. E. Law, H. A. Gelabert

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Background. Dexamethasone (DEX) has been shown to inhibit development of neointimal hyperplasia in rats. We hypothesize that DEX inhibits neointimal hyperplasia by altering matrix metalloproteinase (MMP) activity, resulting in inhibition of smooth muscle cell migration. Methods. Rat aortic smooth muscle cells (RASMC) were harvested and cultured for two to four passages. A migration assay was performed in a Boyden chamber with chemoattractant (platelet-derived growth factor) and varying concentrations of DEX (10-9 to 10-5 M). The number of migrated cells was counted under light microscopy. Zymography was performed on culture media to assess MMP activity, and Western blotting was performed to assay MMP and levels of tissue inhibitors of MMPs (TIMPs). Results. DEX progressively inhibited RASMC migration in a dose-dependent fashion. This effect was statistically significant for concentrations of 10-7 to 10-5 M (P < 0.0005). Zymography showed that DEX inhibits MMP-2 activity in a dose-dependent manner. Western blots indicated that total MMP-2 secretion was inhibited and that TIMP-2 secretion was increased by DEX. Conclusions. DEX inhibits platelet-derived growth factor-induced migration of RASMCs and MMP-2 activity in vitro. Our data suggest that DEX suppresses MMP activity and secretion, resulting in the inhibition of smooth muscle cell migration. This may explain the mechanism by which DEX inhibits neointimal hyperplasia.

Original languageEnglish (US)
Pages (from-to)57-62
Number of pages6
JournalJournal of Surgical Research
Volume102
Issue number2
DOIs
StatePublished - 2002

Keywords

  • Dexamethasone
  • Migration
  • MMP
  • Neointimal hyperplasia
  • Smooth muscle cells
  • TIMP

ASJC Scopus subject areas

  • Surgery

Fingerprint Dive into the research topics of 'Dexamethasone inhibits vascular smooth muscle cell migration via modulation of matrix metalloproteinase activity'. Together they form a unique fingerprint.

  • Cite this

    Pross, C., Farooq, M. M., Angle, N., Lane, J. S., Cerveira, J. J., Xavier, A. E., Freischlag, J. A., Law, R. E., & Gelabert, H. A. (2002). Dexamethasone inhibits vascular smooth muscle cell migration via modulation of matrix metalloproteinase activity. Journal of Surgical Research, 102(2), 57-62. https://doi.org/10.1006/jsre.2001.6220