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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Deletion of the Fc receptors
chain preserves endothelial function affected by hypercholesterolaemia in mice fed on a high-fat diet
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
chain on endothelium-dependent relaxation and oxidative stress after 10 weeks on a high-fat diet in FcR
–/– 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
–/– 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
–/– 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
chain preserves the endothelial function and attenuates oxidative stress affected by hypercholesterolaemia in FcR
–/– 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