Rat and human aortic smooth muscle cells display differing migration and matrix metalloproteinase activities in response to dexamethasone

C. Pross, M. M. Farooq, J. S. Lane, N. Angle, C. K. Tomono, A. E. Xavier, J. A. Freischlag, A. E. Collins, R. E. Law, Hugh A. Gelabert

Research output: Contribution to journalArticle

Abstract

Objective: The steroid dexamethasone inhibits neointimal hyperplasia development in rats but not in humans. This study investigates the differential effects of dexamethasone on rat and human smooth muscle cell migration and matrix metalloproteinase (MMP) activity. Methods: Rat aortic smooth muscle cells were harvested from Sprague-Dawley rats. Human aortic smooth muscle cells were obtained from Clonetics. Boyden chamber migration assays were performed with chemoattractant (platelet-derived growth factor) and varying concentrations of dexamethasone (10-9 to 10-5 mol/L). Zymography of culture media was used to assess MMP activity, and Western blot analysis was used for quantification of MMP-2 and tissue inhibitor of MMP-2 (TIMP-2) secretion. Results: Dexamethasone inhibits rat aortic smooth muscle cell migration in a dose-dependent fashion. An increase in concentrations of dexamethasone does not effect human aortic smooth muscle cell migration. Rat aortic smooth muscle cell MMP-2 activity is inhibited with dexamethasone in a dose-dependent fashion, and human aortic smooth muscle cell MMP-2 activity is unchanged with dexamethasone. MMP-2 secretion is inhibited with dexamethasone in rat aortic smooth muscle cells but remains unaltered in human aortic smooth muscle cells. Dexamethasone increases rat aortic smooth muscle cell TIMP-2 secretion, and human aortic smooth muscle cell TIMP-2 secretion remains constant. Conclusion: Dexamethasone inhibits rat aortic smooth muscle cell migration, MMP-2 activity, and MMP-2 secretion and increases TIMP-2 secretion. These effects are not observed in human aortic smooth muscle cells. These findings may explain why dexamethasone inhibits neointimal hyperplasia in animal models but is ineffective in humans. Inhibition of human smooth muscle cell migration in vitro may be useful in predicting the effectiveness of future therapeutic agents for treatment of neointimal hyperplasia in humans.

Original languageEnglish (US)
Pages (from-to)1253-1259
Number of pages7
JournalJournal of Vascular Surgery
Volume35
Issue number6
DOIs
StatePublished - Jun 2002
Externally publishedYes

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Matrix Metalloproteinases
Dexamethasone
Smooth Muscle Myocytes
Matrix Metalloproteinase 2
Matrix Metalloproteinase Inhibitors
Cell Movement
Hyperplasia
Tissue Inhibitor of Metalloproteinase-2
Muscles
Platelet-Derived Growth Factor
Chemotactic Factors
Sprague Dawley Rats
Culture Media
Animal Models
Western Blotting
Steroids

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Rat and human aortic smooth muscle cells display differing migration and matrix metalloproteinase activities in response to dexamethasone. / Pross, C.; Farooq, M. M.; Lane, J. S.; Angle, N.; Tomono, C. K.; Xavier, A. E.; Freischlag, J. A.; Collins, A. E.; Law, R. E.; Gelabert, Hugh A.

In: Journal of Vascular Surgery, Vol. 35, No. 6, 06.2002, p. 1253-1259.

Research output: Contribution to journalArticle

Pross, C, Farooq, MM, Lane, JS, Angle, N, Tomono, CK, Xavier, AE, Freischlag, JA, Collins, AE, Law, RE & Gelabert, HA 2002, 'Rat and human aortic smooth muscle cells display differing migration and matrix metalloproteinase activities in response to dexamethasone', Journal of Vascular Surgery, vol. 35, no. 6, pp. 1253-1259. https://doi.org/10.1067/mva.2002.123332
Pross, C. ; Farooq, M. M. ; Lane, J. S. ; Angle, N. ; Tomono, C. K. ; Xavier, A. E. ; Freischlag, J. A. ; Collins, A. E. ; Law, R. E. ; Gelabert, Hugh A. / Rat and human aortic smooth muscle cells display differing migration and matrix metalloproteinase activities in response to dexamethasone. In: Journal of Vascular Surgery. 2002 ; Vol. 35, No. 6. pp. 1253-1259.
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abstract = "Objective: The steroid dexamethasone inhibits neointimal hyperplasia development in rats but not in humans. This study investigates the differential effects of dexamethasone on rat and human smooth muscle cell migration and matrix metalloproteinase (MMP) activity. Methods: Rat aortic smooth muscle cells were harvested from Sprague-Dawley rats. Human aortic smooth muscle cells were obtained from Clonetics. Boyden chamber migration assays were performed with chemoattractant (platelet-derived growth factor) and varying concentrations of dexamethasone (10-9 to 10-5 mol/L). Zymography of culture media was used to assess MMP activity, and Western blot analysis was used for quantification of MMP-2 and tissue inhibitor of MMP-2 (TIMP-2) secretion. Results: Dexamethasone inhibits rat aortic smooth muscle cell migration in a dose-dependent fashion. An increase in concentrations of dexamethasone does not effect human aortic smooth muscle cell migration. Rat aortic smooth muscle cell MMP-2 activity is inhibited with dexamethasone in a dose-dependent fashion, and human aortic smooth muscle cell MMP-2 activity is unchanged with dexamethasone. MMP-2 secretion is inhibited with dexamethasone in rat aortic smooth muscle cells but remains unaltered in human aortic smooth muscle cells. Dexamethasone increases rat aortic smooth muscle cell TIMP-2 secretion, and human aortic smooth muscle cell TIMP-2 secretion remains constant. Conclusion: Dexamethasone inhibits rat aortic smooth muscle cell migration, MMP-2 activity, and MMP-2 secretion and increases TIMP-2 secretion. These effects are not observed in human aortic smooth muscle cells. These findings may explain why dexamethasone inhibits neointimal hyperplasia in animal models but is ineffective in humans. Inhibition of human smooth muscle cell migration in vitro may be useful in predicting the effectiveness of future therapeutic agents for treatment of neointimal hyperplasia in humans.",
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T1 - Rat and human aortic smooth muscle cells display differing migration and matrix metalloproteinase activities in response to dexamethasone

AU - Pross, C.

AU - Farooq, M. M.

AU - Lane, J. S.

AU - Angle, N.

AU - Tomono, C. K.

AU - Xavier, A. E.

AU - Freischlag, J. A.

AU - Collins, A. E.

AU - Law, R. E.

AU - Gelabert, Hugh A.

PY - 2002/6

Y1 - 2002/6

N2 - Objective: The steroid dexamethasone inhibits neointimal hyperplasia development in rats but not in humans. This study investigates the differential effects of dexamethasone on rat and human smooth muscle cell migration and matrix metalloproteinase (MMP) activity. Methods: Rat aortic smooth muscle cells were harvested from Sprague-Dawley rats. Human aortic smooth muscle cells were obtained from Clonetics. Boyden chamber migration assays were performed with chemoattractant (platelet-derived growth factor) and varying concentrations of dexamethasone (10-9 to 10-5 mol/L). Zymography of culture media was used to assess MMP activity, and Western blot analysis was used for quantification of MMP-2 and tissue inhibitor of MMP-2 (TIMP-2) secretion. Results: Dexamethasone inhibits rat aortic smooth muscle cell migration in a dose-dependent fashion. An increase in concentrations of dexamethasone does not effect human aortic smooth muscle cell migration. Rat aortic smooth muscle cell MMP-2 activity is inhibited with dexamethasone in a dose-dependent fashion, and human aortic smooth muscle cell MMP-2 activity is unchanged with dexamethasone. MMP-2 secretion is inhibited with dexamethasone in rat aortic smooth muscle cells but remains unaltered in human aortic smooth muscle cells. Dexamethasone increases rat aortic smooth muscle cell TIMP-2 secretion, and human aortic smooth muscle cell TIMP-2 secretion remains constant. Conclusion: Dexamethasone inhibits rat aortic smooth muscle cell migration, MMP-2 activity, and MMP-2 secretion and increases TIMP-2 secretion. These effects are not observed in human aortic smooth muscle cells. These findings may explain why dexamethasone inhibits neointimal hyperplasia in animal models but is ineffective in humans. Inhibition of human smooth muscle cell migration in vitro may be useful in predicting the effectiveness of future therapeutic agents for treatment of neointimal hyperplasia in humans.

AB - Objective: The steroid dexamethasone inhibits neointimal hyperplasia development in rats but not in humans. This study investigates the differential effects of dexamethasone on rat and human smooth muscle cell migration and matrix metalloproteinase (MMP) activity. Methods: Rat aortic smooth muscle cells were harvested from Sprague-Dawley rats. Human aortic smooth muscle cells were obtained from Clonetics. Boyden chamber migration assays were performed with chemoattractant (platelet-derived growth factor) and varying concentrations of dexamethasone (10-9 to 10-5 mol/L). Zymography of culture media was used to assess MMP activity, and Western blot analysis was used for quantification of MMP-2 and tissue inhibitor of MMP-2 (TIMP-2) secretion. Results: Dexamethasone inhibits rat aortic smooth muscle cell migration in a dose-dependent fashion. An increase in concentrations of dexamethasone does not effect human aortic smooth muscle cell migration. Rat aortic smooth muscle cell MMP-2 activity is inhibited with dexamethasone in a dose-dependent fashion, and human aortic smooth muscle cell MMP-2 activity is unchanged with dexamethasone. MMP-2 secretion is inhibited with dexamethasone in rat aortic smooth muscle cells but remains unaltered in human aortic smooth muscle cells. Dexamethasone increases rat aortic smooth muscle cell TIMP-2 secretion, and human aortic smooth muscle cell TIMP-2 secretion remains constant. Conclusion: Dexamethasone inhibits rat aortic smooth muscle cell migration, MMP-2 activity, and MMP-2 secretion and increases TIMP-2 secretion. These effects are not observed in human aortic smooth muscle cells. These findings may explain why dexamethasone inhibits neointimal hyperplasia in animal models but is ineffective in humans. Inhibition of human smooth muscle cell migration in vitro may be useful in predicting the effectiveness of future therapeutic agents for treatment of neointimal hyperplasia in humans.

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