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Apolipoprotein B of low-density lipoprotein impairs nitric oxide-mediated endothelium-dependent relaxation in rat mesenteric arteries

Zhang, Yaping LU ; Zhang, Wei; Edvinsson, Lars LU and Xu, Cang-Bao LU (2014) In European Journal of Pharmacology 725(Jan 18). p.10-17
Abstract
Apolipoprotein B (ApoB) of low-density lipoprotein (LDL) causes endothelial dysfunction in the initial stage of atherogenesis. The present study was designed to explore the underlying molecular mechanisms involved. Rat mesenteric arteries were organ cultured in the presence of different concentrations of ApoB or LDL. Vasodilation induced by acetylcholine was monitored by a sensitive myograph. Nitric oxide (NO), endothelium-dependent hyperpolarizing factor (EDHF) and prostacyclin (PGI2) pathways were characterized by using specific pathway inhibitors. Real-time PCR and immunohistochemistry with confocal microscopy were used to examine alteration of mRNA and protein expressions for NO synthases (eNOS and iNOS) and cycloxygenase (COX),... (More)
Apolipoprotein B (ApoB) of low-density lipoprotein (LDL) causes endothelial dysfunction in the initial stage of atherogenesis. The present study was designed to explore the underlying molecular mechanisms involved. Rat mesenteric arteries were organ cultured in the presence of different concentrations of ApoB or LDL. Vasodilation induced by acetylcholine was monitored by a sensitive myograph. Nitric oxide (NO), endothelium-dependent hyperpolarizing factor (EDHF) and prostacyclin (PGI2) pathways were characterized by using specific pathway inhibitors. Real-time PCR and immunohistochemistry with confocal microscopy were used to examine alteration of mRNA and protein expressions for NO synthases (eNOS and iNOS) and cycloxygenase (COX), respectively. Lipid peroxidation was measured by thiobarbituric acid reactive substances. In the presence of either LDL or ApoB for 24h concentration-dependently attenuated the endothelium-dependent vasodilation. Immunohistochemistry staining of endothelial cell marker CD31 was weaker in the presence of LDL, indicating that LDL induced damage to the endothelium. Using the pathway specific inhibitors demonstrated that LDL-induced impairing vasodilation was mainly due to attenuation of NO pathway. This was supported by decreasing mRNA (real-time PCR) and protein expression (immunohistochemistry) for eNOS and iNOS, but not COX, in the presence of LDL. In addition, the levels of lipid peroxidation significantly increased in the presence of LDL for 24h. In conclusion, ApoB of LDL impairs vasodilation with damaging the endothelium and attenuating the NO-mediated endothelium-dependent relaxation, which might associate with lipid peroxidation and contribute to the development of cardiovascular disease. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Pharmacology
volume
725
issue
Jan 18
pages
10 - 17
publisher
Elsevier
external identifiers
  • pmid:24444440
  • wos:000331140900002
  • scopus:84893190774
ISSN
1879-0712
DOI
10.1016/j.ejphar.2014.01.008
language
English
LU publication?
yes
id
91ff9908-7f4a-4562-a11f-6c0554fe4ead (old id 4291042)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24444440?dopt=Abstract
date added to LUP
2014-02-07 16:09:10
date last changed
2017-02-26 03:23:42
@article{91ff9908-7f4a-4562-a11f-6c0554fe4ead,
  abstract     = {Apolipoprotein B (ApoB) of low-density lipoprotein (LDL) causes endothelial dysfunction in the initial stage of atherogenesis. The present study was designed to explore the underlying molecular mechanisms involved. Rat mesenteric arteries were organ cultured in the presence of different concentrations of ApoB or LDL. Vasodilation induced by acetylcholine was monitored by a sensitive myograph. Nitric oxide (NO), endothelium-dependent hyperpolarizing factor (EDHF) and prostacyclin (PGI2) pathways were characterized by using specific pathway inhibitors. Real-time PCR and immunohistochemistry with confocal microscopy were used to examine alteration of mRNA and protein expressions for NO synthases (eNOS and iNOS) and cycloxygenase (COX), respectively. Lipid peroxidation was measured by thiobarbituric acid reactive substances. In the presence of either LDL or ApoB for 24h concentration-dependently attenuated the endothelium-dependent vasodilation. Immunohistochemistry staining of endothelial cell marker CD31 was weaker in the presence of LDL, indicating that LDL induced damage to the endothelium. Using the pathway specific inhibitors demonstrated that LDL-induced impairing vasodilation was mainly due to attenuation of NO pathway. This was supported by decreasing mRNA (real-time PCR) and protein expression (immunohistochemistry) for eNOS and iNOS, but not COX, in the presence of LDL. In addition, the levels of lipid peroxidation significantly increased in the presence of LDL for 24h. In conclusion, ApoB of LDL impairs vasodilation with damaging the endothelium and attenuating the NO-mediated endothelium-dependent relaxation, which might associate with lipid peroxidation and contribute to the development of cardiovascular disease.},
  author       = {Zhang, Yaping and Zhang, Wei and Edvinsson, Lars and Xu, Cang-Bao},
  issn         = {1879-0712},
  language     = {eng},
  number       = {Jan 18},
  pages        = {10--17},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Apolipoprotein B of low-density lipoprotein impairs nitric oxide-mediated endothelium-dependent relaxation in rat mesenteric arteries},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2014.01.008},
  volume       = {725},
  year         = {2014},
}