Osteopontin deficiency dampens the pro-atherogenic effect of uraemia

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Kardiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)

Nyckelord

Uraemia

Atherosclerosis

Osteopontin

5

6 Nephrectomy

Mouse

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)