Advanced

Minimally modified LDL upregulates endothelin type B receptors in rat coronary artery via ERK1/2 MAPK and NF-kappa B pathways

Li, Jie; Cao, Yong-Xiao; Yuan, Zu-Yi and Xu, Cang-Bao LU (2012) In Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids 1821(4). p.582-589
Abstract
Minimally modified low density lipoprotein (mmLDL) is a well-known risk factor for coronary artery disease. Upregulation of vascular endothelin type B (ETB) receptors on the vascular smooth muscle cells is predicted to be the molecular mechanism that leads to cardiovascular pathogenesis. The objective of the present study was to examine the hypothesis that mmLDL upregulates ETB receptors in rat coronary artery. The contractile responses to sarafotoxin 6c (ETB receptor agonist) were studied using a sensitive myograph. ETB receptor mRNA and protein expression was determined using real-time PCR and Western blot analysis. The results showed that organ culture increased the contractile responses induced by sarafotoxin 6c and the levels of ETB... (More)
Minimally modified low density lipoprotein (mmLDL) is a well-known risk factor for coronary artery disease. Upregulation of vascular endothelin type B (ETB) receptors on the vascular smooth muscle cells is predicted to be the molecular mechanism that leads to cardiovascular pathogenesis. The objective of the present study was to examine the hypothesis that mmLDL upregulates ETB receptors in rat coronary artery. The contractile responses to sarafotoxin 6c (ETB receptor agonist) were studied using a sensitive myograph. ETB receptor mRNA and protein expression was determined using real-time PCR and Western blot analysis. The results showed that organ culture increased the contractile responses induced by sarafotoxin 6c and the levels of ETB receptor mRNA and protein. This increase was further enhanced by the addition of mmLDL (10 mu g/mL). Specific ERK1/2 inhibitors (SB386023 and U0126) and an NF-kappa B inhibitor (wedelolactone) attenuated the mmLDL-increased ETB receptor-mediated contraction and ETB receptor mRNA and protein levels. Wedelolactone significantly attenuated the mmLDL-decreased I kappa B-alpha protein expression. Consistent with this result, I kappa B-alpha protein expression was significantly decreased by culture with mmLDL compared to the level of expression in the organ culture group. However, the JNK inhibitor, SP600125 or p38 pathway inhibitor, SB203580 did not inhibit mmLDL-enhanced effects. The PKC inhibitor, staurosporine attenuated only culture-alone-increased effects. In conclusion, mmLDL upregulates the ETB receptors in rat coronary arterial smooth muscle cells, mainly via activation of the ERK1/2 MAPK and the downstream transcriptional factor NF-kappa B. (C) 2011 Elsevier B.V. All rights reserved. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Minimally modified low density lipoprotein, Coronary artery, Endothelin, type B receptor, Extracellular signal related kinases 1/2, Nuclear, factor-kappa B
in
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
volume
1821
issue
4
pages
582 - 589
publisher
Elsevier
external identifiers
  • wos:000302486500003
  • scopus:84857671380
ISSN
1388-1981
DOI
10.1016/j.bbalip.2011.12.001
language
English
LU publication?
yes
id
62ab6719-1c56-448f-9889-b7631053c786 (old id 2587589)
date added to LUP
2012-06-01 09:38:51
date last changed
2017-10-01 04:21:42
@article{62ab6719-1c56-448f-9889-b7631053c786,
  abstract     = {Minimally modified low density lipoprotein (mmLDL) is a well-known risk factor for coronary artery disease. Upregulation of vascular endothelin type B (ETB) receptors on the vascular smooth muscle cells is predicted to be the molecular mechanism that leads to cardiovascular pathogenesis. The objective of the present study was to examine the hypothesis that mmLDL upregulates ETB receptors in rat coronary artery. The contractile responses to sarafotoxin 6c (ETB receptor agonist) were studied using a sensitive myograph. ETB receptor mRNA and protein expression was determined using real-time PCR and Western blot analysis. The results showed that organ culture increased the contractile responses induced by sarafotoxin 6c and the levels of ETB receptor mRNA and protein. This increase was further enhanced by the addition of mmLDL (10 mu g/mL). Specific ERK1/2 inhibitors (SB386023 and U0126) and an NF-kappa B inhibitor (wedelolactone) attenuated the mmLDL-increased ETB receptor-mediated contraction and ETB receptor mRNA and protein levels. Wedelolactone significantly attenuated the mmLDL-decreased I kappa B-alpha protein expression. Consistent with this result, I kappa B-alpha protein expression was significantly decreased by culture with mmLDL compared to the level of expression in the organ culture group. However, the JNK inhibitor, SP600125 or p38 pathway inhibitor, SB203580 did not inhibit mmLDL-enhanced effects. The PKC inhibitor, staurosporine attenuated only culture-alone-increased effects. In conclusion, mmLDL upregulates the ETB receptors in rat coronary arterial smooth muscle cells, mainly via activation of the ERK1/2 MAPK and the downstream transcriptional factor NF-kappa B. (C) 2011 Elsevier B.V. All rights reserved.},
  author       = {Li, Jie and Cao, Yong-Xiao and Yuan, Zu-Yi and Xu, Cang-Bao},
  issn         = {1388-1981},
  keyword      = {Minimally modified low density lipoprotein,Coronary artery,Endothelin,type B receptor,Extracellular signal related kinases 1/2,Nuclear,factor-kappa B},
  language     = {eng},
  number       = {4},
  pages        = {582--589},
  publisher    = {Elsevier},
  series       = {Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids},
  title        = {Minimally modified LDL upregulates endothelin type B receptors in rat coronary artery via ERK1/2 MAPK and NF-kappa B pathways},
  url          = {http://dx.doi.org/10.1016/j.bbalip.2011.12.001},
  volume       = {1821},
  year         = {2012},
}