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Transcriptional Down-Regulation of Thromboxane A(2) Receptor Expression via Activation of MAPK ERK1/2, p38/NF-kappa B Pathways

Zhang, Wei; Zhang, Yaping LU ; Edvinsson, Lars LU and Xu, Cang-Bao LU (2009) In Journal of Vascular Research1992-01-01+01:00 46(2). p.162-174
Abstract
Background: We have developed an in vitro model by organ culture of rat mesenteric arteries to imitate vascular smooth muscle cell (VSMC) receptor changes in cardiovascular disease. By using this model, alteration of VSMC thromboxane A(2) (TP) receptors was studied. Methods and Results: After organ culture of the arteries, VSMC TP receptors were studied by using myography, real-time PCR and immunohistochemistry. We observed that organ culture for 24 and 48 h resulted in depressed TP receptor-mediated contraction in the VSMC, in parallel with decreased TP receptor mRNA and protein expressions. Phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 and nuclear factor-kappa B (NF-kappa B) was seen by Western blot... (More)
Background: We have developed an in vitro model by organ culture of rat mesenteric arteries to imitate vascular smooth muscle cell (VSMC) receptor changes in cardiovascular disease. By using this model, alteration of VSMC thromboxane A(2) (TP) receptors was studied. Methods and Results: After organ culture of the arteries, VSMC TP receptors were studied by using myography, real-time PCR and immunohistochemistry. We observed that organ culture for 24 and 48 h resulted in depressed TP receptor-mediated contraction in the VSMC, in parallel with decreased TP receptor mRNA and protein expressions. Phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 and nuclear factor-kappa B (NF-kappa B) was seen by Western blot within 1-3 h after organ culture. Inhibition of ERK1/2, p38 or NF-kappa B reversed depressed contraction as well as decreased receptor mRNA expression. Actinomycin D abolished decreased TP receptor-mediated contraction, while inhibition of translation, cyclooxygenase or nitric oxide synthase had no effect. TP receptor mRNA stability was unchanged during organ culture. Conclusions: The present study has demonstrated for the first time that organ culture of rat mesenteric arteries down-regulates VSMC TP receptor expression through activation of ERK1/2 and p38/NF-kappa B signal pathways. Copyright (C) 2008 S. Karger AG, Basel (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Vascular diseases, Rat, Thromboxane A(2) receptors, Mesenteric artery
in
Journal of Vascular Research1992-01-01+01:00
volume
46
issue
2
pages
162 - 174
publisher
Karger
external identifiers
  • wos:000263696900008
  • scopus:50649118327
  • pmid:18769070
ISSN
1423-0135
DOI
10.1159/000153247
language
English
LU publication?
yes
id
f0bcc8a9-6e94-42be-b470-818b142ba89d (old id 1371065)
date added to LUP
2009-05-08 17:20:34
date last changed
2017-01-01 06:33:52
@article{f0bcc8a9-6e94-42be-b470-818b142ba89d,
  abstract     = {Background: We have developed an in vitro model by organ culture of rat mesenteric arteries to imitate vascular smooth muscle cell (VSMC) receptor changes in cardiovascular disease. By using this model, alteration of VSMC thromboxane A(2) (TP) receptors was studied. Methods and Results: After organ culture of the arteries, VSMC TP receptors were studied by using myography, real-time PCR and immunohistochemistry. We observed that organ culture for 24 and 48 h resulted in depressed TP receptor-mediated contraction in the VSMC, in parallel with decreased TP receptor mRNA and protein expressions. Phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 and nuclear factor-kappa B (NF-kappa B) was seen by Western blot within 1-3 h after organ culture. Inhibition of ERK1/2, p38 or NF-kappa B reversed depressed contraction as well as decreased receptor mRNA expression. Actinomycin D abolished decreased TP receptor-mediated contraction, while inhibition of translation, cyclooxygenase or nitric oxide synthase had no effect. TP receptor mRNA stability was unchanged during organ culture. Conclusions: The present study has demonstrated for the first time that organ culture of rat mesenteric arteries down-regulates VSMC TP receptor expression through activation of ERK1/2 and p38/NF-kappa B signal pathways. Copyright (C) 2008 S. Karger AG, Basel},
  author       = {Zhang, Wei and Zhang, Yaping and Edvinsson, Lars and Xu, Cang-Bao},
  issn         = {1423-0135},
  keyword      = {Vascular diseases,Rat,Thromboxane A(2) receptors,Mesenteric artery},
  language     = {eng},
  number       = {2},
  pages        = {162--174},
  publisher    = {Karger},
  series       = {Journal of Vascular Research1992-01-01+01:00},
  title        = {Transcriptional Down-Regulation of Thromboxane A(2) Receptor Expression via Activation of MAPK ERK1/2, p38/NF-kappa B Pathways},
  url          = {http://dx.doi.org/10.1159/000153247},
  volume       = {46},
  year         = {2009},
}