PMID- 11795999
OWN - NLM
STAT- MEDLINE
DCOM- 20020221
LR  - 20181130
IS  - 0022-4804 (Print)
IS  - 0022-4804 (Linking)
VI  - 102
IP  - 2
DP  - 2002 Feb
TI  - Dexamethasone inhibits vascular smooth muscle cell migration via modulation of 
      matrix metalloproteinase activity.
PG  - 57-62
AB  - 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.
CI  - (c)2001 Elsevier Science.
FAU - Pross, C
AU  - Pross C
AD  - Division of Vascular Surgery, University of California-Los Angeles Medical 
      Center, Los Angeles, California 90096, USA.
FAU - Farooq, M M
AU  - Farooq MM
FAU - Angle, N
AU  - Angle N
FAU - Lane, J S
AU  - Lane JS
FAU - Cerveira, J J
AU  - Cerveira JJ
FAU - Xavier, A E
AU  - Xavier AE
FAU - Freischlag, J A
AU  - Freischlag JA
FAU - Law, R E
AU  - Law RE
FAU - Gelabert, H A
AU  - Gelabert HA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Surg Res
JT  - The Journal of surgical research
JID - 0376340
RN  - 0 (Glucocorticoids)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Animals
MH  - Aorta/cytology
MH  - Apoptosis/drug effects
MH  - Cell Movement/drug effects
MH  - Cells, Cultured
MH  - Dexamethasone/*pharmacology
MH  - Enzyme Activation/drug effects
MH  - Glucocorticoids/*pharmacology
MH  - Matrix Metalloproteinase 2/*metabolism
MH  - Muscle, Smooth, Vascular/*cytology/enzymology/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tissue Inhibitor of Metalloproteinase-2/metabolism
EDAT- 2002/02/14 10:00
MHDA- 2002/02/22 10:01
CRDT- 2002/02/14 10:00
PHST- 2002/02/14 10:00 [pubmed]
PHST- 2002/02/22 10:01 [medline]
PHST- 2002/02/14 10:00 [entrez]
AID - S0022480401962201 [pii]
AID - 10.1006/jsre.2001.6220 [doi]
PST - ppublish
SO  - J Surg Res. 2002 Feb;102(2):57-62. doi: 10.1006/jsre.2001.6220.