title: Osteopontin deficiency dampens the pro-atherogenic effect of uraemia.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  The data suggest that OPN promotes development of uraemic atherosclerosis possibly by changing the phenotype of vascular smooth muscle cells.
authors: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark. tanjax@sund.ku.dk
authors: Tanja X
authors: TX
authors: Pedersen
authors: Marie
authors: M
authors: Madsen
authors: Nanna
authors: N
authors: Junker
authors: Christina
authors: C
authors: Christoffersen
authors: Jonas
authors: J
authors: Vikeså
authors: Susanne
authors: S
authors: Bro
authors: Anna
authors: A
authors: Hultgårdh-Nilsson
authors: Lars Bo
authors: LB
authors: Nielsen
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000517:prevention & control*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D054337:Cell Dedifferentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005838:Genotype; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D009392:Nephrectomy; D053495:Osteopontin / Q000172:deficiency* / Q000235:genetics; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D014511:Uremia / Q000150:complications* / Q000235:genetics / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; C506896:Spp1 protein, mouse; D053495:Osteopontin
keywords: 5/6 Nephrectomy; Atherosclerosis; Mouse; Osteopontin; Uraemia