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Cardiovascular Research Advance Access [Accepted Manuscript] published online on August 11, 2008

Cardiovascular Research, 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 Hypercholesterolemia in Mice Fed on a High-fat Diet

Katsuhiko Sumiyoshi, PhD, Hiroshi Mokuno, MD, Takafumi Iesaki, MD, Kazunori Shimada, MD, Tetsuro Miyazaki, MD, Atsumi Kume, MD, Takashi Kiyanagi, MD, Kenichi Kuremoto, MD, Yoshiro Watanabe, MD, Nobuhiro Tada, PhD* and Hiroyuki Daida, MD

From Department of Cardiology, Atopy Research Center Juntendo University School of Medicine, Japan

Correspondence to; Hiroshi Mokuno, MD, Department of Cardiology, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan Voice: +81-3-5802-1056 FAX: +81-3-5689-0627 E-mail: hiromokt{at}par.odn.ne.jp

Aims: To clarify the role of Fc receptors (FcR) for immunoglobulin in endothelial dysfunction induced by hypercholesterolemia, 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 wild-type mice.

Methods and Results: Plasma cholesterol levels on the high-fat diet were significantly increased compared with the levels on the normal chow diet in both groups of mice. Endothelium-dependent relaxation of the aortic ring to acetylcholine in wild-type mice was significantly reduced by the high-fat diet (ED50: 0.22 nM vs. 0.43 nM, P <0.002), whereas the relaxation in FcR {gamma} -/- mice was not inhibited (ED50: 0.22 nM 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 stress 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 deletion of the FcR {gamma} chain preserves endothelial function and attenuates oxidative stress affected by hypercholesterolemia in FcR {gamma} -/- mice. These results indicate that FcR may play the pivotal role in endothelial dysfunction through oxidative stress induced by hypercholesterolemia.


Time for primary review: 29 days

* Atopy Research Center Juntendo University School of Medicine, Japan


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