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  • 标题:Lipid-soluble cigarette smoking particles induce expression of inflammatory and extracellular-matrix-related genes in rat cerebral arteries
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  • 作者:Petter Vikman ; Cang-Bao Xu ; Lars Edvinsson
  • 期刊名称:Vascular Health and Risk Management
  • 印刷版ISSN:1176-6344
  • 电子版ISSN:1178-2048
  • 出版年度:2009
  • 卷号:5
  • 页码:333-341
  • DOI:10.2147/VHRM.S4866
  • 出版社:Dove Medical Press Ltd
  • 摘要: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 μl/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 (AT1 and AT2), 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 AT1 receptors, but not of AT2 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 AT1 receptor expression in the cerebral arteries, which are key events in stroke pathogenesis.
  • 关键词:cigarette smoking; vascular inflammation; signal transduction; extracellular matrix; MMP; stroke
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