Osteopontin transgenic mice fed a high-cholesterol diet develop early fatty-streak lesions.
BACKGROUND
Osteopontin (OPN) is a noncollagenous adhesion protein found at the site of atherosclerotic lesions. However, it has not yet been clarified whether or not OPN can promote atherosclerotic lesions. METHODS AND RESULTS We investigated the contribution of OPN to atherosclerosis by evaluating aortic sinus lesions of both OPN transgenic (Tg) and non-Tg mice fed an atherogenic diet (1.25% cholesterol) for 16 weeks. The atherosclerotic lesions were found to be significantly larger in OPN-Tg compared with those in non-Tg (17,859+/-2010 versus 6469+/-485 micro m(2), P<0.01). The lesions in both mice were fatty-streak lesions with an accumulation of mononuclear cells and lipids. We next investigated the production of interleukin (IL)-10 by macrophages from both mice. Compared with the non-Tg mice, a 42% (P<0.01) and 73% (P<0.001) decrease in the IL-10 production was identified in the OPN-Tg mice either without or with lipopolysaccharide.


CONCLUSIONS
The expression of OPN induces fatty-streak lesion formation in mice fed an atherogenic diet and inhibits IL-10 production by macrophages, thus suggesting that OPN plays an important role in the development of fatty-streak lesions in vivo.
Isoda
Kikuo
K
Internal Medicine I, National Defense Medical College, Tokorozawa, Saitama, Japan. isoda@me.ndmc.ac.jp
Kamezawa
Yashuhiro
Y
Ayaori
Makoto
M
Kusuhara
Masatoshi
M
Tada
Norihiro
N
Ohsuzu
Fumitaka
F
D000818:Animals; D001161:Arteriosclerosis / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D002791:Cholesterol, Dietary; D004036:Diet, Atherogenic; D018450:Disease Progression; D016753:Interleukin-10 / Q000096:biosynthesis; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000235:genetics*; D012850:Sinus of Valsalva / Q000473:pathology
D002791:Cholesterol, Dietary; D008055:Lipids; D008070:Lipopolysaccharides; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D016753:Interleukin-10