IFN-gamma deficiency exerts gender-specific effects on atherogenesis in apolipoprotein E-/- mice.
We have shown recently that administration of exogenous interferon-gamma (IFN-gamma) to apolipoprotein E (apoE)(-/-) mice augmented atherogenesis. In the present study, we examined whether deficiency of endogenous IFN-gamma would reduce atherosclerosis in apoE(-/-) mice. Compound-deficient mice were generated by crossing strain-matched IFN-gamma(-/-) and apoE(-/-) mice and comparing them to apoE(-/-) mice. Groups of both genders were fed either a normal or a high-fat diet. IFN-gamma deficiency did not affect serum cholesterol concentrations or lipoprotein-cholesterol distributions in any groups. IFN-gamma deficiency had no effect on serum triglyceride concentrations, except for an increase noted in males fed a normal diet. The extent of atherosclerosis was determined in tissue sections of the ascending aorta and on the surface of the aortic arch. During feeding of normal diets, IFN-gamma deficiency had no effect on the extent of atherosclerosis in female mice in either vascular bed. In contrast, in male mice fed normal diet, IFN-gamma deficiency markedly decreased lesion size in both vascular beds. During feeding of high-fat diets, IFN-gamma deficiency also had no effect on lesion size in females but profoundly decreased lesion size in the aortic root of male mice. IFN-gamma deficiency had no effect on the abundance of T lymphocytes or MHC class II-positive cells in aortic root lesions of females. By comparison, both these parameters were reduced in lesions of male mice. Therefore, IFN-gamma deficiency decreased atherogenesis, potentially by decreasing T lymphocyte presence and cell activation, without influencing serum cholesterol concentrations. However, this effect is strikingly restricted to male mice.
Whitman
Stewart C
SC
University of Ottawa Heart Institute, Ottawa, Ontario, Canada, K1Y 4W7.
Ravisankar
Punnaivanam
P
Daugherty
Alan
A
D000818:Animals; D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001013:Aorta, Thoracic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D005260:Female; D005802:Genes, MHC Class II; D007371:Interferon-gamma / Q000172:deficiency*; D008074:Lipoproteins / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012737:Sex Factors; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008074:Lipoproteins; D014280:Triglycerides; D007371:Interferon-gamma; D002784:Cholesterol