IFN-gamma deficiency exerts gender-specific effects on atherogenesis in apolipoprotein E-/- mice.

• Abstract: 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.
• Authors: Stewart C Whitman, Punnaivanam Ravisankar, Alan Daugherty (Affiliation: University of Ottawa Heart Institute, Ottawa, Ontario, Canada, K1Y 4W7.)
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 22 Issue 6 Pg. 661-70 (Jun 2002) ISSN: 1079-9907 [Print] United States
• PMID: 12162876 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Lipoproteins
• Triglycerides
• Cholesterol
• Interferon-gamma

Topics

• Animals
• Aorta (immunology, metabolism, pathology)
• Aorta, Thoracic (immunology, metabolism, pathology)
• Apolipoproteins E (genetics)
• Arteriosclerosis (genetics, immunology, pathology)
• Cholesterol (blood)
• Diet, Atherogenic
• Female
• Genes, MHC Class II
• Interferon-gamma (deficiency)
• Lipoproteins (blood)
• Lymphocyte Activation
• Male
• Mice
• Mice, Knockout
• Sex Factors
• T-Lymphocytes (immunology)
• Time Factors
• Triglycerides (blood)