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Reduction of bFGF-induced smooth muscle cell proliferation and endothelin receptor mRNA expression by mevastatin and atorvastatin.

Xu, Cang Bao ; Stenman, Emelie LU and Edvinsson, Lars LU (2002) In Biochemical Pharmacology 64(3). p.497-505
Abstract
The anti-atherosclerosis mechanisms of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) occur via both cholesterol-dependent and cholesterol-independent mechanisms. The present study used aortic and cerebral vascular smooth muscle cells (SMC) from rat to investigate whether atorvastatin and mevastatin affect basic fibroblast growth factor (bFGF)-induced SMC proliferation and the mRNA expression of endothelin A (ET(A)) and endothelin B (ET(B)) receptors. Cell proliferation was assessed by MTT and real-time PCR was used to quantify ET(A) and ET(B) receptor mRNA. bFGF-induced concentration and time dependent SMC proliferation and up-regulation of the mRNA expression of ET(A) and ET(B) receptors. The... (More)
The anti-atherosclerosis mechanisms of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) occur via both cholesterol-dependent and cholesterol-independent mechanisms. The present study used aortic and cerebral vascular smooth muscle cells (SMC) from rat to investigate whether atorvastatin and mevastatin affect basic fibroblast growth factor (bFGF)-induced SMC proliferation and the mRNA expression of endothelin A (ET(A)) and endothelin B (ET(B)) receptors. Cell proliferation was assessed by MTT and real-time PCR was used to quantify ET(A) and ET(B) receptor mRNA. bFGF-induced concentration and time dependent SMC proliferation and up-regulation of the mRNA expression of ET(A) and ET(B) receptors. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors inhibited bFGF-induced proliferation of SMC (P<0.01). In aortic SMC atorvastatin and mevastatin significantly inhibited bFGF-induced mRNA expression of endothelin ET(A) and ET(B) receptors (P<0.05). Although in cerebral SMC the inhibitory effect of the statins was comparable in size with that seen in aortic SMC, only reached borderline significance (P=0.06) for ET(A) receptor mRNA but not for ET(B). The findings suggested a direct effect of statins on the vascular wall beyond their well-known lipid lowering effect in anti-atherosclerosis. Furthermore, the specific antagonists of ET(A) and ET(B) receptors (FR139317 and BQ788, respectively) significantly inhibited bFGF-induced SMC proliferation (P<0.001). The results suggested that endothelin receptors and the mevalonate pathway were involved in bFGF-induced SMC proliferation. (Less)
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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemical Pharmacology
volume
64
issue
3
pages
497 - 505
publisher
Elsevier
external identifiers
  • pmid:12147302
  • wos:000177602900018
  • scopus:0036685160
ISSN
0006-2952
DOI
10.1016/S0006-2952(02)01189-9
language
English
LU publication?
yes
id
7d9bee68-8e0b-4e21-a643-2c3eeb5309cb (old id 109669)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12147302&dopt=Abstract
date added to LUP
2016-04-01 12:29:02
date last changed
2024-01-08 22:02:07
@article{7d9bee68-8e0b-4e21-a643-2c3eeb5309cb,
  abstract     = {{The anti-atherosclerosis mechanisms of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) occur via both cholesterol-dependent and cholesterol-independent mechanisms. The present study used aortic and cerebral vascular smooth muscle cells (SMC) from rat to investigate whether atorvastatin and mevastatin affect basic fibroblast growth factor (bFGF)-induced SMC proliferation and the mRNA expression of endothelin A (ET(A)) and endothelin B (ET(B)) receptors. Cell proliferation was assessed by MTT and real-time PCR was used to quantify ET(A) and ET(B) receptor mRNA. bFGF-induced concentration and time dependent SMC proliferation and up-regulation of the mRNA expression of ET(A) and ET(B) receptors. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors inhibited bFGF-induced proliferation of SMC (P&lt;0.01). In aortic SMC atorvastatin and mevastatin significantly inhibited bFGF-induced mRNA expression of endothelin ET(A) and ET(B) receptors (P&lt;0.05). Although in cerebral SMC the inhibitory effect of the statins was comparable in size with that seen in aortic SMC, only reached borderline significance (P=0.06) for ET(A) receptor mRNA but not for ET(B). The findings suggested a direct effect of statins on the vascular wall beyond their well-known lipid lowering effect in anti-atherosclerosis. Furthermore, the specific antagonists of ET(A) and ET(B) receptors (FR139317 and BQ788, respectively) significantly inhibited bFGF-induced SMC proliferation (P&lt;0.001). The results suggested that endothelin receptors and the mevalonate pathway were involved in bFGF-induced SMC proliferation.}},
  author       = {{Xu, Cang Bao and Stenman, Emelie and Edvinsson, Lars}},
  issn         = {{0006-2952}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{497--505}},
  publisher    = {{Elsevier}},
  series       = {{Biochemical Pharmacology}},
  title        = {{Reduction of bFGF-induced smooth muscle cell proliferation and endothelin receptor mRNA expression by mevastatin and atorvastatin.}},
  url          = {{http://dx.doi.org/10.1016/S0006-2952(02)01189-9}},
  doi          = {{10.1016/S0006-2952(02)01189-9}},
  volume       = {{64}},
  year         = {{2002}},
}