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Cardiovascular Research Advance Access originally published online on August 11, 2008
Cardiovascular Research 2008 80(3):463-470; doi:10.1093/cvr/cvn206
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Deletion of the Fc receptors {gamma} chain preserves endothelial function affected by hypercholesterolaemia in mice fed on a high-fat diet

Katsuhiko Sumiyoshi1, Hiroshi Mokuno1,*, Takafumi Iesaki1, Kazunori Shimada1, Tetsuro Miyazaki1, Atsumi Kume1, Takashi Kiyanagi1, Kenichi Kuremoto1, Yoshiro Watanabe1, Nobuhiro Tada2 and Hiroyuki Daida1

1 Department of Cardiology, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
2 Atopy Research Center, Juntendo University School of Medicine, Japan

* Corresponding author. Tel: +81 3 5802 1056; fax: +81 3 5689 0627. E-mail address: hiromokt{at}par.odn.ne.jp

Aims: To clarify the role of Fc receptors (FcR) for immunoglobulin in endothelial dysfunction induced by hypercholesterolaemia, we evaluated the effect of deletion of the FcR {gamma} chain on endothelium-dependent relaxation and oxidative stress after 10 weeks on a high-fat diet in FcR {gamma}–/– mice compared with that in wild-type mice.

Methods and results: Plasma cholesterol levels of those on the high-fat diet were significantly increased compared with those on the normal chow diet in both groups of mice. Endothelium-dependent relaxation of the aortic ring with acetylcholine in wild-type mice was significantly reduced by the high-fat diet (ED50: 0.22 vs. 0.43 nM, P < 0.002), whereas the relaxation in FcR {gamma}–/– mice was not inhibited (ED50: 0.22 vs. 0.23 nM, NS). Furthermore, superoxide detection by dihydroethidium-derived fluorescence and immunohistochemical staining of p22phox expression were significantly increased in wild-type mice fed on the high-fat diet, while these oxidative stresses in FcR {gamma}–/– mice were not enhanced by the high-fat diet. Oil Red O-staining showed no significant lipid accumulation at the aortic sinus in both groups of mice.

Conclusion: This study demonstrates that the deletion of the FcR {gamma} chain preserves the endothelial function and attenuates oxidative stress affected by hypercholesterolaemia in FcR {gamma}–/– mice. These results indicate that FcR may play the pivotal role in endothelial dysfunction through oxidative stress induced by hypercholesterolaemia.

KEYWORDS Fc receptors; Endothelial function; Hypercholesterolaemia; p22phox; Oxidative stress


Time for primary review: 29 days


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