on May 1, 2003
Arteriosclerosis, Thrombosis, and Vascular Biology. 2003
Published online before print May 1, 2003, doi: 10.1161/01.ATV.0000074878.29805.D0
Published online before print May 1, 2003, doi: 10.1161/01.ATV.0000074878.29805.D0
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Submitted on January 7, 2003
Accepted on April 14, 2003
Osteopontin Deficiency Attenuates Atherosclerosis in Female Apolipoprotein E-Deficient Mice
Yutaka Matsui ;
From the Division of Molecular Immunology (Y.M., M.I., J.M., C.K., S.K., T.U.), Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan; Department of Cardiovascular Medicine (Y.M., H.O., N.J., T.S., M.A., T.S., A.K.), Hokkaido University Graduate School of Medicine, Sapporo, Japan; and Departments of Genetics (S.R.R.) and Cell Biology and Neuroscience (D.D.), Rutgers University, Piscataway, NJ.
* To whom correspondence should be addressed. E-mail: toshi{at}imm.hokudai.ac.jp.
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.
Methods and 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.
Key words: osteopontin • atherosclerosis • macrophage • calcification • lipid metabolism
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