IFN-gamma potentiates atherosclerosis in ApoE knock-out mice.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

IFN-gamma potentiates atherosclerosis in ApoE knock-out mice.

J Clin Invest. 1997 Jun 1;99(11):2752-61. Unique Identifier : AIDSLINE MED/97313512
Gupta S; Pablo AM; Jiang Xc; Wang N; Tall AR; Schindler C; Department of Medicine, Columbia University, New York 10032, USA.

Abstract: The early colocalization of T cells and the potent immunostimulatory cytokine IFN-gamma to atherosclerotic lesions suggest that the immune system contributes to atherogenesis. Since mice with a targeted disruption of the apoE gene (apoE 0 mice) develop profound atherosclerosis, we examined the role of IFN-gamma in this process. First, the presence of CD4(+) and CD8(+) cells, which secrete lesional IFN-gamma, was documented in apoE 0 atheromata. Then, the apoE 0 mice were crossed with IFN-gamma receptor (IFNgammaR) 0 mice to generate apoE 0/IFNgammaR 0 mice. Compared to the apoE 0 mice, the compound knock-out mice exhibited a substantial reduction in atherosclerotic lesion size, a 60% reduction in lesion lipid accumulation, a decrease in lesion cellularity, but a marked increase in lesion collagen content. Evaluation of the plasma lipoproteins showed that the compound knockout mice had a marked increase in potentially atheroprotective phospholipid/apoA-IV rich particles as well. This correlated with an induction of hepatic apoA-IV transcripts. These observations suggest that IFN-gamma promotes and modifies atherosclerosis through both local effects in the arterial wall as well as a systemic effect on plasma lipoproteins. Therefore, therapeutic inhibition of IFN-gamma signaling may lead to the formation of more lipid-poor and stable atheromata.

Keywords: *Apolipoproteins E/DEFICIENCY *Atherosclerosis/IMMUNOLOGY *CD4-Positive T-Lymphocytes/IMMUNOLOGY *CD8-Positive T-Lymphocytes/IMMUNOLOGY *Interferon Type II/IMMUNOLOGY
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