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

Cardiovasc Res. 2008 Dec 1;80(3):463-70. doi: 10.1093/cvr/cvn206. Epub 2008 Aug 11.

Abstract

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 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.

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 (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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Dietary Fats / adverse effects*
  • Endothelium, Vascular / metabolism*
  • Gene Deletion*
  • Hypercholesterolemia / etiology
  • Hypercholesterolemia / metabolism*
  • Hypercholesterolemia / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitroprusside / pharmacology
  • Oxidative Stress / physiology
  • Receptors, IgG / genetics*
  • Receptors, IgG / metabolism*
  • Superoxides / metabolism
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology

Substances

  • Dietary Fats
  • Receptors, IgG
  • Vasodilator Agents
  • Superoxides
  • Nitroprusside
  • Acetylcholine