Cardiovascular Research Advance Access [Accepted Manuscript] published online on August 11, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn206
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Deletion of the Fc Receptors
Chain Preserves Endothelial Function Affected by Hypercholesterolemia in Mice Fed on a High-fat Diet
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
chain on endothelium-dependent relaxation and oxidative stress after 10 weeks on a high-fat diet in FcR
-/- 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
-/- 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
-/- 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
chain preserves endothelial function and attenuates oxidative stress affected by hypercholesterolemia in FcR
-/- 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