Osteopontin deficiency dampens the pro-atherogenic effect of uraemia

Tanja Xenia Pedersen; Marie Madsen; Nanna Maria Junker Nielsen; Christina Christoffersen; Jonas Vikeså; Susanne Bro; Anna Hultgårdh-Nilsson; Lars Bo Nielsen

doi:10.1093/cvr/cvt049

Osteopontin deficiency dampens the pro-atherogenic effect of uraemia

Tanja Xenia Pedersen, Marie Madsen, Nanna Maria Junker Nielsen, Christina Christoffersen, Jonas Vikeså, Susanne Bro, Anna Hultgårdh-Nilsson, Lars Bo Nielsen

15 Citations (Scopus)

Abstract

AimsUraemia 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.Methods and resultsUraemia 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 (r² = 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.ConclusionThe data suggest that OPN promotes development of uraemic atherosclerosis possibly by changing the phenotype of vascular smooth muscle cells.

Original language	English
Journal	Cardiovascular Research
Volume	98
Issue number	3
Pages (from-to)	352-9
Number of pages	8
ISSN	0008-6363
DOIs	https://doi.org/10.1093/cvr/cvt049
Publication status	Published - 1 Jun 2013

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@article{f95cec699d344c289cadb9af04325b40,

title = "Osteopontin deficiency dampens the pro-atherogenic effect of uraemia",

abstract = "AimsUraemia 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.Methods and resultsUraemia 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 (r2 = 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.ConclusionThe data suggest that OPN promotes development of uraemic atherosclerosis possibly by changing the phenotype of vascular smooth muscle cells.",

author = "Pedersen, {Tanja Xenia} and Marie Madsen and Nielsen, {Nanna Maria Junker} and Christina Christoffersen and Jonas Vikes{\aa} and Susanne Bro and Anna Hultg{\aa}rdh-Nilsson and Nielsen, {Lars Bo}",

year = "2013",

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doi = "10.1093/cvr/cvt049",

language = "English",

volume = "98",

pages = "352--9",

journal = "Cardiovascular Research",

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T1 - Osteopontin deficiency dampens the pro-atherogenic effect of uraemia

AU - Pedersen, Tanja Xenia

AU - Madsen, Marie

AU - Nielsen, Nanna Maria Junker

AU - Christoffersen, Christina

AU - Vikeså, Jonas

AU - Bro, Susanne

AU - Hultgårdh-Nilsson, Anna

AU - Nielsen, Lars Bo

PY - 2013/6/1

Y1 - 2013/6/1

N2 - AimsUraemia 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.Methods and resultsUraemia 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 (r2 = 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.ConclusionThe data suggest that OPN promotes development of uraemic atherosclerosis possibly by changing the phenotype of vascular smooth muscle cells.

AB - AimsUraemia 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.Methods and resultsUraemia 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 (r2 = 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.ConclusionThe data suggest that OPN promotes development of uraemic atherosclerosis possibly by changing the phenotype of vascular smooth muscle cells.

U2 - 10.1093/cvr/cvt049

DO - 10.1093/cvr/cvt049

M3 - Journal article

C2 - 23455547

SN - 0008-6363

VL - 98

SP - 352

EP - 359

JO - Cardiovascular Research

JF - Cardiovascular Research

IS - 3

ER -

Osteopontin deficiency dampens the pro-atherogenic effect of uraemia

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