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Lipid-soluble cigarette smoking particles induce expression of inflammatory and extracellular-matrix-related genes in rat cerebral arteries.

Vikman, Petter LU ; Xu, Cang-Bao LU and Edvinsson, Lars LU (2009) In Vascular Health and Risk Management 5(1). p.333-341
Abstract
AIMS: Cigarette smoking is one of the strongest risk factors for stroke. However, the underlying molecular mechanisms that smoke leads to the pathogenesis of stroke are incompletely understood. METHODS: Dimethyl sulfoxide (DMSO)-soluble (lipid-soluble) cigarette smoking particles (DSP) were extracted from cigarette smoke (0.8 mg nicotine per cigarette; Marlboro). Rat cerebral arteries were isolated and organ cultured in the presence of DSP (0.2 microl/ml, equivalent to the plasma level in smokers) for 24 h. The expression of matrix metalloproteinase 9 and 13 (MMP9 and MMP13), angiotensin receptor 1 and 2 (AT(1) and AT(2)), interleukin 6 and inducible nitric oxide synthase (iNOS) were investigated at mRNA level by real-time PCR and/or at... (More)
AIMS: Cigarette smoking is one of the strongest risk factors for stroke. However, the underlying molecular mechanisms that smoke leads to the pathogenesis of stroke are incompletely understood. METHODS: Dimethyl sulfoxide (DMSO)-soluble (lipid-soluble) cigarette smoking particles (DSP) were extracted from cigarette smoke (0.8 mg nicotine per cigarette; Marlboro). Rat cerebral arteries were isolated and organ cultured in the presence of DSP (0.2 microl/ml, equivalent to the plasma level in smokers) for 24 h. The expression of matrix metalloproteinase 9 and 13 (MMP9 and MMP13), angiotensin receptor 1 and 2 (AT(1) and AT(2)), interleukin 6 and inducible nitric oxide synthase (iNOS) were investigated at mRNA level by real-time PCR and/or at protein level by immunohistochemistry. In addition, the activity of three mitogen-activated protein kinases (p38, ERK 1/2 and SAPK/JNK) and their downstream transcription factors (ATF-2, Elk-1 and c-Jun) were examined. RESULTS: We observed that compared with control (DMSO-treated cerebral arteries), the cerebral arteries treated by DSP exhibited enhanced expression of MMP13 and AT(1) receptors, but not of AT(2) receptors, at both mRNA and protein levels, suggesting that a transcriptional mechanism is most likely involved in the DSP effects. This is further supported by the findings that DSP induced phosphorylation of p38 mitogen-activated protein kinases inflammatory signal protein in parallel with activation of its downstream transcription factor ATF-2 and Elk-1. However, ERK 1/2 and SAPK/JNK activities were markedly expressed in the control (organ culture per se with DMSO), and DSP failed to further enhance the activation of ERK 1/2 and SAPK/JNK in the cerebral arteries. CONCLUSIONS: DSP induces cerebral vessel inflammation with activation of p38 MAPK inflammatory signal and the downstream transcriptional factors (ATF-2 and Elk-1) in parallel with enhanced extracellular-matrix-related gene transcription and increased AT(1) receptor expression in the cerebral arteries, which are key events in stroke pathogenesis. (Less)
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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Vascular Health and Risk Management
volume
5
issue
1
pages
333 - 341
publisher
Dove Medical Press Ltd.
external identifiers
  • pmid:19436652
  • scopus:67449084386
ISSN
1178-2048
language
English
LU publication?
yes
id
b5c6dd80-de7b-491f-a0d2-2b72c26989e1 (old id 1412368)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19436652?dopt=Abstract
date added to LUP
2016-04-04 08:51:39
date last changed
2024-10-12 19:11:15
@article{b5c6dd80-de7b-491f-a0d2-2b72c26989e1,
  abstract     = {{AIMS: Cigarette smoking is one of the strongest risk factors for stroke. However, the underlying molecular mechanisms that smoke leads to the pathogenesis of stroke are incompletely understood. METHODS: Dimethyl sulfoxide (DMSO)-soluble (lipid-soluble) cigarette smoking particles (DSP) were extracted from cigarette smoke (0.8 mg nicotine per cigarette; Marlboro). Rat cerebral arteries were isolated and organ cultured in the presence of DSP (0.2 microl/ml, equivalent to the plasma level in smokers) for 24 h. The expression of matrix metalloproteinase 9 and 13 (MMP9 and MMP13), angiotensin receptor 1 and 2 (AT(1) and AT(2)), interleukin 6 and inducible nitric oxide synthase (iNOS) were investigated at mRNA level by real-time PCR and/or at protein level by immunohistochemistry. In addition, the activity of three mitogen-activated protein kinases (p38, ERK 1/2 and SAPK/JNK) and their downstream transcription factors (ATF-2, Elk-1 and c-Jun) were examined. RESULTS: We observed that compared with control (DMSO-treated cerebral arteries), the cerebral arteries treated by DSP exhibited enhanced expression of MMP13 and AT(1) receptors, but not of AT(2) receptors, at both mRNA and protein levels, suggesting that a transcriptional mechanism is most likely involved in the DSP effects. This is further supported by the findings that DSP induced phosphorylation of p38 mitogen-activated protein kinases inflammatory signal protein in parallel with activation of its downstream transcription factor ATF-2 and Elk-1. However, ERK 1/2 and SAPK/JNK activities were markedly expressed in the control (organ culture per se with DMSO), and DSP failed to further enhance the activation of ERK 1/2 and SAPK/JNK in the cerebral arteries. CONCLUSIONS: DSP induces cerebral vessel inflammation with activation of p38 MAPK inflammatory signal and the downstream transcriptional factors (ATF-2 and Elk-1) in parallel with enhanced extracellular-matrix-related gene transcription and increased AT(1) receptor expression in the cerebral arteries, which are key events in stroke pathogenesis.}},
  author       = {{Vikman, Petter and Xu, Cang-Bao and Edvinsson, Lars}},
  issn         = {{1178-2048}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{333--341}},
  publisher    = {{Dove Medical Press Ltd.}},
  series       = {{Vascular Health and Risk Management}},
  title        = {{Lipid-soluble cigarette smoking particles induce expression of inflammatory and extracellular-matrix-related genes in rat cerebral arteries.}},
  url          = {{http://www.ncbi.nlm.nih.gov/pubmed/19436652?dopt=Abstract}},
  volume       = {{5}},
  year         = {{2009}},
}