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


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 (ED(50): 0.22 vs. 0.43 nM, P < 0.002), whereas the relaxation in FcR gamma(-/-) mice was not inhibited (ED(50): 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.


CONCLUSIONS
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.
Sumiyoshi
Katsuhiko
K
Department of Cardiology, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Mokuno
Hiroshi
H
Iesaki
Takafumi
T
Shimada
Kazunori
K
Miyazaki
Tetsuro
T
Kume
Atsumi
A
Kiyanagi
Takashi
T
Kuremoto
Kenichi
K
Watanabe
Yoshiro
Y
Tada
Nobuhiro
N
Daida
Hiroyuki
H
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000378:metabolism*; D017353:Gene Deletion; D006937:Hypercholesterolemia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D004041:Dietary Fats; D017452:Receptors, IgG; D014665:Vasodilator Agents; D013481:Superoxides; D009599:Nitroprusside; D000109:Acetylcholine