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Osteopontin deficiency dampens the pro-atherogenic effect of uraemia

Pedersen, Tanja X.; Madsen, Marie; Junker, Nanna; Christoffersen, Christina; Vikesa, Jonas; Bro, Susanne; Hultgårdh, Anna LU and Nielsen, Lars Bo (2013) In Cardiovascular Research 98(3). p.352-359
Abstract
Uraemia is a strong risk factor for cardiovascular disease. Osteopontin (OPN) is highly expressed in aortas of uraemic apolipoprotein E knockout (E KO) mice. OPN affects key atherogenic processes, i.e. inflammation and phenotypic modulation of smooth muscle cells (SMCs). We explored the role of OPN on vascular pathology in uraemic mice. Uraemia was induced by 5/6 nephrectomy in E KO and in OPN and E double KO mice (E/OPN KO). In E KO mice, uraemia increased the relative surface plaque area in the aortic arch (from 28 2 [n 15], to 37 3 [n 20] of the aortic arch area, P 0.05). A positive correlation was observed between plasma OPN and aortic atherosclerosis in uraemic E KO mice (r(2) 0.48, P 0.001). In contrast, aortic atherosclerosis was... (More)
Uraemia is a strong risk factor for cardiovascular disease. Osteopontin (OPN) is highly expressed in aortas of uraemic apolipoprotein E knockout (E KO) mice. OPN affects key atherogenic processes, i.e. inflammation and phenotypic modulation of smooth muscle cells (SMCs). We explored the role of OPN on vascular pathology in uraemic mice. Uraemia was induced by 5/6 nephrectomy in E KO and in OPN and E double KO mice (E/OPN KO). In E KO mice, uraemia increased the relative surface plaque area in the aortic arch (from 28 2 [n 15], to 37 3 [n 20] of the aortic arch area, P 0.05). A positive correlation was observed between plasma OPN and aortic atherosclerosis in uraemic E KO mice (r(2) 0.48, P 0.001). In contrast, aortic atherosclerosis was not increased by uraemia in E/OPN KO mice. OPN deficiency in haematopoietic cells (including macrophages) did not affect development of uraemic atherosclerosis, even though OPN-deficient foam cells had decreased inflammatory capacity. Gene expression analyses indicated that uraemia de-differentiates SMCs in the arterial wall. This effect was dampened in whole-body OPN-deficient mice. The data suggest that OPN promotes development of uraemic atherosclerosis possibly by changing the phenotype of vascular smooth muscle cells. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Uraemia, Atherosclerosis, Osteopontin, 5, 6 Nephrectomy, Mouse
in
Cardiovascular Research
volume
98
issue
3
pages
352 - 359
publisher
Elsevier
external identifiers
  • wos:000319428700005
  • scopus:84877942003
ISSN
1755-3245
DOI
10.1093/cvr/cvt049
language
English
LU publication?
yes
id
c5c09903-a42b-45c5-a085-81bd70e0fd46 (old id 3930675)
date added to LUP
2013-08-01 07:37:27
date last changed
2019-01-06 04:34:47
@article{c5c09903-a42b-45c5-a085-81bd70e0fd46,
  abstract     = {Uraemia is a strong risk factor for cardiovascular disease. Osteopontin (OPN) is highly expressed in aortas of uraemic apolipoprotein E knockout (E KO) mice. OPN affects key atherogenic processes, i.e. inflammation and phenotypic modulation of smooth muscle cells (SMCs). We explored the role of OPN on vascular pathology in uraemic mice. Uraemia was induced by 5/6 nephrectomy in E KO and in OPN and E double KO mice (E/OPN KO). In E KO mice, uraemia increased the relative surface plaque area in the aortic arch (from 28 2 [n 15], to 37 3 [n 20] of the aortic arch area, P 0.05). A positive correlation was observed between plasma OPN and aortic atherosclerosis in uraemic E KO mice (r(2) 0.48, P 0.001). In contrast, aortic atherosclerosis was not increased by uraemia in E/OPN KO mice. OPN deficiency in haematopoietic cells (including macrophages) did not affect development of uraemic atherosclerosis, even though OPN-deficient foam cells had decreased inflammatory capacity. Gene expression analyses indicated that uraemia de-differentiates SMCs in the arterial wall. This effect was dampened in whole-body OPN-deficient mice. The data suggest that OPN promotes development of uraemic atherosclerosis possibly by changing the phenotype of vascular smooth muscle cells.},
  author       = {Pedersen, Tanja X. and Madsen, Marie and Junker, Nanna and Christoffersen, Christina and Vikesa, Jonas and Bro, Susanne and Hultgårdh, Anna and Nielsen, Lars Bo},
  issn         = {1755-3245},
  keyword      = {Uraemia,Atherosclerosis,Osteopontin,5,6 Nephrectomy,Mouse},
  language     = {eng},
  number       = {3},
  pages        = {352--359},
  publisher    = {Elsevier},
  series       = {Cardiovascular Research},
  title        = {Osteopontin deficiency dampens the pro-atherogenic effect of uraemia},
  url          = {http://dx.doi.org/10.1093/cvr/cvt049},
  volume       = {98},
  year         = {2013},
}