Osteopontin deficiency dampens the pro-atherogenic effect of uraemia
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3930675
- author
- Pedersen, Tanja X. ; Madsen, Marie ; Junker, Nanna ; Christoffersen, Christina ; Vikesa, Jonas ; Bro, Susanne ; Hultgårdh, Anna LU and Nielsen, Lars Bo
- organization
- publishing date
- 2013
- 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
- Oxford University Press
- 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
- 2016-04-01 10:40:39
- date last changed
- 2022-04-04 20:16:46
@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}}, keywords = {{Uraemia; Atherosclerosis; Osteopontin; 5; 6 Nephrectomy; Mouse}}, language = {{eng}}, number = {{3}}, pages = {{352--359}}, publisher = {{Oxford University Press}}, series = {{Cardiovascular Research}}, title = {{Osteopontin deficiency dampens the pro-atherogenic effect of uraemia}}, url = {{http://dx.doi.org/10.1093/cvr/cvt049}}, doi = {{10.1093/cvr/cvt049}}, volume = {{98}}, year = {{2013}}, }