Osteopontin deficiency attenuates atherosclerosis in female apolipoprotein E-deficient mice.
OBJECTIVE
Osteopontin (OPN), a noncollagenous adhesive protein, is implicated in atherosclerosis, in which macrophages within atherosclerotic plaques express OPN. However, it is not known whether the elevated OPN expression is a cause or result of atherosclerosis.


RESULTS
We generated mice that lacked OPN and crossed them with apolipoprotein (apo) E-deficient mice and analyzed these mice with a mixed C57BL/6x129 background after 36 weeks on a normal chow diet. In female mice, OP+/-E-/- and OP-/-E-/- mice had significantly smaller atherosclerotic and inflammatory lesions compared with OP+/+E-/- mice, and that was reflected by smaller area of MOMA-2-positive staining. In male mice, however, there was no significant difference in the atherosclerosis lesion areas among 3 genotypes. In both OP-/-E-/- and OP+/+E-/- mice, typical atherosclerotic lesions were detected, which include necrotic core, foamy cell collections, and cholesterol clefts. However, we found that vascular mineral-deposited areas in 60-week-old male OP-/-E-/- mice were significantly increased compared with those in OP+/+E-/- male mice.


CONCLUSIONS
These results suggest that OPN plays a promoting effect in atherosclerosis and inhibitory effect in vascular calcification. The suppression of OPN expression in females should be considered a therapeutic possibility in atherosclerosis.
Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan.
Yutaka
Y
Matsui
Susan R
SR
Rittling
Hiroshi
H
Okamoto
Manabu
M
Inobe
Nan
N
Jia
Toshihiro
T
Shimizu
Masatoshi
M
Akino
Takeshi
T
Sugawara
Junko
J
Morimoto
Chiemi
C
Kimura
Shigeyuki
S
Kon
David
D
Denhardt
Akira
A
Kitabatake
Toshimitsu
T
Uede
D000818:Animals; D001018:Aortic Diseases / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001161:Arteriosclerosis / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D002114:Calcinosis / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D003433:Crosses, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D008055:Lipids / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014657:Vasculitis / Q000235:genetics / Q000473:pathology / Q000517:prevention & control
D001057:Apolipoproteins E; D008055:Lipids; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin