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Low density lipoprotein induces upregulation of vasoconstrictive endothelin type B receptor expression.

Xu, Cang-Bao LU ; Zheng, Jianpu LU ; Zhang, Wei LU ; Liu, Enqi; Edvinsson, Lars LU and Zhang, Yaping LU (2014) In Vascular Pharmacology 60(1). p.42-48
Abstract
Vasoconstrictive endothelin type B (ETB) receptors promote vasospasm and ischemic cerebro- and cardiovascular diseases. The present study was designed to examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive ETB receptor expression and if extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) signal pathways are involved in this process. Rat mesenteric artery segments were organ cultured in the presence and absence of LDL with or without inhibitors for MAPK kinase 1 and 2 (MEK1/2), p38 and transcription. The upregulation of vasoconstrictive ETB receptor expression was studied using a sensitive myograph, real-time PCR and Western blot. LDL (11, 22 and 44mg... (More)
Vasoconstrictive endothelin type B (ETB) receptors promote vasospasm and ischemic cerebro- and cardiovascular diseases. The present study was designed to examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive ETB receptor expression and if extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) signal pathways are involved in this process. Rat mesenteric artery segments were organ cultured in the presence and absence of LDL with or without inhibitors for MAPK kinase 1 and 2 (MEK1/2), p38 and transcription. The upregulation of vasoconstrictive ETB receptor expression was studied using a sensitive myograph, real-time PCR and Western blot. LDL (11, 22 and 44mg protein/L) concentration-dependently induced upregulation of vasoconstrictive ETB receptor expression with increase in the receptor-mediated vasoconstriction, elevated levels of the ETB receptor mRNA and protein expressions, and activation of ERK1/2 and p38 MAPK. Blockage of ERK1/2 and p38 MAPK signal pathways using MEK1/2 inhibitors (PD98059 and U0126) or p38 inhibitors (SB203580 and SB239063) significantly abolished the LDL-induced upregulation of vasoconstrictive ETB receptor expression. Actinomycin D (general transcriptional inhibitor) almost completely inhibited the LDL effects. In conclusion, LDL induces upregulation of vasoconstrictive ETB receptor expression through activation of ERK1/2 and p38 MAPK signal pathway-dependent transcriptional mechanisms. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Vascular Pharmacology
volume
60
issue
1
pages
42 - 48
publisher
Elsevier
external identifiers
  • pmid:24315856
  • wos:000330600100006
  • scopus:84892493929
ISSN
1537-1891
DOI
10.1016/j.vph.2013.11.004
language
English
LU publication?
yes
id
603afb83-2ca0-4754-a0f6-7d3244008a43 (old id 4225057)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24315856?dopt=Abstract
date added to LUP
2014-01-03 14:20:29
date last changed
2017-06-25 03:09:13
@article{603afb83-2ca0-4754-a0f6-7d3244008a43,
  abstract     = {Vasoconstrictive endothelin type B (ETB) receptors promote vasospasm and ischemic cerebro- and cardiovascular diseases. The present study was designed to examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive ETB receptor expression and if extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) signal pathways are involved in this process. Rat mesenteric artery segments were organ cultured in the presence and absence of LDL with or without inhibitors for MAPK kinase 1 and 2 (MEK1/2), p38 and transcription. The upregulation of vasoconstrictive ETB receptor expression was studied using a sensitive myograph, real-time PCR and Western blot. LDL (11, 22 and 44mg protein/L) concentration-dependently induced upregulation of vasoconstrictive ETB receptor expression with increase in the receptor-mediated vasoconstriction, elevated levels of the ETB receptor mRNA and protein expressions, and activation of ERK1/2 and p38 MAPK. Blockage of ERK1/2 and p38 MAPK signal pathways using MEK1/2 inhibitors (PD98059 and U0126) or p38 inhibitors (SB203580 and SB239063) significantly abolished the LDL-induced upregulation of vasoconstrictive ETB receptor expression. Actinomycin D (general transcriptional inhibitor) almost completely inhibited the LDL effects. In conclusion, LDL induces upregulation of vasoconstrictive ETB receptor expression through activation of ERK1/2 and p38 MAPK signal pathway-dependent transcriptional mechanisms.},
  author       = {Xu, Cang-Bao and Zheng, Jianpu and Zhang, Wei and Liu, Enqi and Edvinsson, Lars and Zhang, Yaping},
  issn         = {1537-1891},
  language     = {eng},
  number       = {1},
  pages        = {42--48},
  publisher    = {Elsevier},
  series       = {Vascular Pharmacology},
  title        = {Low density lipoprotein induces upregulation of vasoconstrictive endothelin type B receptor expression.},
  url          = {http://dx.doi.org/10.1016/j.vph.2013.11.004},
  volume       = {60},
  year         = {2014},
}