RGD Reference Report - Osteopontin deficiency attenuates atherosclerosis in female apolipoprotein E-deficient mice. - Rat Genome Database

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Osteopontin deficiency attenuates atherosclerosis in female apolipoprotein E-deficient mice.

Authors: Matsui, Y  Rittling, SR  Okamoto, H  Inobe, M  Jia, N  Shimizu, T  Akino, M  Sugawara, T  Morimoto, J  Kimura, C  Kon, S  Denhardt, D  Kitabatake, A  Uede, T 
Citation: Matsui Y, etal., Arterioscler Thromb Vasc Biol. 2003 Jun 1;23(6):1029-34. Epub 2003 May 1.
RGD ID: 1581357
Pubmed: PMID:12730087   (View Abstract at PubMed)
DOI: DOI:10.1161/01.ATV.0000074878.29805.D0   (Journal Full-text)

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.

Objects referenced in this article
Gene SPP1 secreted phosphoprotein 1 Homo sapiens
Gene Spp1 secreted phosphoprotein 1 Mus musculus
Gene Spp1 secreted phosphoprotein 1 Rattus norvegicus

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