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

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
Externally publishedYes

Fingerprint

Matrix Metalloproteinases
Vascular Smooth Muscle
Dexamethasone
Smooth Muscle Myocytes
Cell Movement
Matrix Metalloproteinase 2
Hyperplasia
Matrix Metalloproteinase Inhibitors
Platelet-Derived Growth Factor
Western Blotting
Chemotactic Factors
Culture Media
Microscopy
Cell Count
Light

Keywords

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

ASJC Scopus subject areas

  • Surgery

Cite this

Pross, C., Farooq, M. M., Angle, N., Lane, J. S., Cerveira, J. J., Xavier, A. 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

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

In: Journal of Surgical Research, Vol. 102, No. 2, 2002, p. 57-62.

Research output: Contribution to journalArticle

Pross, C, Farooq, MM, Angle, N, Lane, JS, Cerveira, JJ, Xavier, AE, Freischlag, JA, Law, RE & Gelabert, HA 2002, 'Dexamethasone inhibits vascular smooth muscle cell migration via modulation of matrix metalloproteinase activity', Journal of Surgical Research, vol. 102, no. 2, pp. 57-62. https://doi.org/10.1006/jsre.2001.6220
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. / Dexamethasone inhibits vascular smooth muscle cell migration via modulation of matrix metalloproteinase activity. In: Journal of Surgical Research. 2002 ; Vol. 102, No. 2. pp. 57-62.
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