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

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 γ chain on endothelium-dependent relaxation and oxidative stress after 10 weeks on a high-fat diet in FcR γ−/− 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 γ−/− 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 γ−/− 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 γ chain preserves the endothelial function and attenuates oxidative stress affected by hypercholesterolaemia in FcR γ−/− mice. These results indicate that FcR may play the pivotal role in endothelial dysfunction through oxidative stress induced by hypercholesterolaemia.